Ronald P Hammer

Interests

Research

Neuropsychiatric disorders; Brain mechanisms underlying schizophrenia; Stress and drug addiction; Cell signaling and gonadal steroid hormone biology.

Teaching

Clinical Neurosciences, Clinical Anatomy; Mentoring Philosophy: I strive to utilize best practices in mentoring at all levels by determining and aligning expectations on both sides of the relationship, assessing mentee knowledge and capabilities to live up to their highest potential, incorporating self-reflection to better address mentor bias(es) and promote inclusive practices, establishing optimal communication approaches with mentees, building confidence and fostering their independence, and promoting professional development to expand their career potential.

Courses

Scholarly Contributions

Chapters

• Miczek, K. A., Nikulina, E. M., Covington, H. E., & Hammer, R. P. (2003). Social conflict: gene expression in aminergic and peptidergic cells during aggression and defeat. In "Nurturing the Genome. A Festschrift for Benson E. Ginsburg,".
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  Editors: S.C. Maxson and R. Buck
• Hammer, R. P. (2002). Neural circuitry and signaling in addiction. In Brain Circuitry and Signaling in Psychiatry; Basic Science and Clinical Implications(pp 99-124). American Psychiatric Publishing Inc.
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  Editors: G.B. Kaplan and R.P. Hammer

Journals/Publications

• Rudolph, M. L., Neve, R. L., Hammer, R. P., & Nikulina, E. M. (2022). Enhanced psychostimulant response, but not social avoidance, depends on GluA1 AMPA receptors in VTA dopamine neurons following intermittent social defeat stress in rats. The European Journal of Neuroscience, 55(9-10), 2154-2169.
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  Evidence from both human and animal studies demonstrates the importance of social stress in the development of addiction-related behaviour. In rats, intermittent social defeat stress causes long-lasting psychostimulant cross-sensitization. Our recent data reveal heightened expression of AMPA receptor (AMPAR) GluA1 subunit in rat ventral tegmental area (VTA), which occurs concurrently with social stress-induced amphetamine (AMPH) cross-sensitization. In addition, social stress in rats induced social avoidance behaviour. The present study evaluated the effects of intermittent social defeat stress on GluA1 expression in VTA dopamine (DA) neurons, then utilized Cre-dependent virus-mediated gene transfer to determine the functional role of homomeric GluA1-AMPARs in these neurons. Social defeat stress exposure induced GluA1 expression in VTA DA neurons, as demonstrated by a greater density of GluA1/tyrosine hydroxylase (TH) double-labelling in VTA neurons in stressed rats. Additionally, functional inactivation of VTA GluA1 AMPARs in DA neurons prevented stress-induced cross-sensitization, or augmented locomotor response to low dose AMPH challenge (1.0 mg/kg, i.p.), but had no effect on social stress-induced social avoidance behaviour. Furthermore, wild-type overexpression of GluA1 in VTA DA neurons had the opposite effect; locomotor-activating effects of AMPH were significantly augmented, even in the absence of stress. Taken together, these results suggest that stress-induced GluA1 expression in VTA DA neurons is necessary for psychostimulant cross-sensitization, but not for social avoidance. This differential effect suggests that different neural pathways are implicated in these behaviours. These findings could lead to novel pharmacotherapies to help prevent stress-induced susceptibility to substance abuse.
• Rudolph, M. L., Neve, R. L., Hammer, R. P., & Nikulina, E. M. (2020). Enhanced psychostimulant response, but not social avoidance, depends on GluA1 AMPA receptors in VTA dopamine neurons following intermittent social defeat stress in rats. Eur J Neurosci, Online ahead of print.. doi:10.1111/ejn.14884
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  Evidence from both human and animal studies demonstrates the importance of social stress in the development of addiction-related behaviour. In rats, intermittent social defeat stress causes long-lasting psychostimulant cross-sensitization. Our recent data reveal heightened expression of AMPA receptor (AMPAR) GluA1 subunit in rat ventral tegmental area (VTA), which occurs concurrently with social stress-induced amphetamine (AMPH) cross-sensitization. In addition, social stress in rats induced social avoidance behaviour. The present study evaluated the effects of intermittent social defeat stress on GluA1 expression in VTA dopamine (DA) neurons, then utilized Cre-dependent virus-mediated gene transfer to determine the functional role of homomeric GluA1-AMPARs in these neurons. Social defeat stress exposure induced GluA1 expression in VTA DA neurons, as demonstrated by a greater density of GluA1/tyrosine hydroxylase (TH) double-labelling in VTA neurons in stressed rats. Additionally, functional inactivation of VTA GluA1 AMPARs in DA neurons prevented stress-induced cross-sensitization, or augmented locomotor response to low dose AMPH challenge (1.0 mg/kg, i.p.), but had no effect on social stress-induced social avoidance behaviour. Furthermore, wild-type overexpression of GluA1 in VTA DA neurons had the opposite effect; locomotor-activating effects of AMPH were significantly augmented, even in the absence of stress. Taken together, these results suggest that stress-induced GluA1 expression in VTA DA neurons is necessary for psychostimulant cross-sensitization, but not for social avoidance. This differential effect suggests that different neural pathways are implicated in these behaviours. These findings could lead to novel pharmacotherapies to help prevent stress-induced susceptibility to substance abuse.
• Hammer, R. P., Call, T., Kimmel, P. C., & Maple, A. M. (2017). Effects of repeated D2-like agonist treatment on phencyclidine-induced hyperlocomotion, prepulse inhibition deficits, and social avoidance in rats. Journal of Pharmacology and Experimental Therapeutics, 361, 109-114.
• Huang, Z., Shen, J., Wang, J., Wang, H., Zhang, H., Gao, M., Hammer, R. P., Fan, X., & Wu, J. (2015). Selective activation of cannabimoid receptor subtype 2 (CB2R) eliminates agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells. Acta pharmacologica Sinica.
• Huang, Z., Wang, H., Wang, J., Zhao, M., Sun, N., Sun, F., Shen, J., Zhang, H., Xia, K., Chen, D., Gao, M., Hammer, R. P., Liu, Q., Xi, Z., Fan, X., & Wu, J. (2016). Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca(2+) oscillations in mouse pancreatic acinar cells. Scientific reports, 6, 29757.
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  Emerging evidence demonstrates that the blockade of intracellular Ca(2+) signals may protect pancreatic acinar cells against Ca(2+) overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca(2+) signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca(2+) oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca(2+) oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca(2+) oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca(2+) oscillations and L-arginine-induced enhancement of Ca(2+) signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis.
• Hoffman, A. N., Parga, A., Paode, P., Watterson, L., Nikulina, E. M., Hammer, R. P., & Conrad, C. D. (2015). Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation. Neurobiology of Memory and Learning, 120, 61-68.
• Huang, Z., Wang, H., Sun, N., Wang, J., Zhao, M., Shen, J., Gao, M., Hammer, R. P., Fan, X., & Wu, J. (2014). Congo red modulates ACh-induced Ca(2+) oscillations in single pancreatic acinar cells of mice. Acta pharmacologica Sinica, 35(12), 1514-20.
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  Congo red, a secondary diazo dye, is usually used as an indicator for the presence of amyloid fibrils. Recent studies show that congo red exerts neuroprotective effects in a variety of models of neurodegenerative diseases. However, its pharmacological profile remains unknown. In this study, we investigated the effects of congo red on ACh-induced Ca(2+) oscillations in mouse pancreatic acinar cells in vitro.
• Johnston, C. E., Herschl, D. J., Lasek, A. W., Hammer, R. P., & Nikulina, E. M. (2014). Knockdown of ventral tegmental area mu-opioid receptors in rats prevents effects of social defeat stress: Implications for amphetamine cross-sensitization, social avoidance, weight regulation and expression of brain-derived neurotrophic factor. Neuropharmacology, 89, 325-334.
• Nikulina, E. M., Johnston, C., Wang, J., & Hammer, R. P. (2014). Neurotrophins in the ventral tegmental area: role in social stress, mood disorders and drug abuse. Neuroscience, 282, 122-138.
• Wang, J., Bina, R. W., Wingard, J. C., Terwilliger, E. F., Hammer, R. P., & Nikulina, E. M. (2014). Knockdown of tropomyosin-related kinase B receptor expression in the nucleus accumbens shell prevents intermittent social defeat stress-induced cross-sensitization to amphetamine in rats. European Journal of Neuroscience, 39(6), 1009-1017.
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  The nucleus accumbens (NAc) is a critical brain region for the rewarding effects of drugs of abuse. Brain-derived neurotrophic factor (BDNF) can facilitate stress- and drug-induced neuroadaptation in the mesocorticolimbic system. BDNF-containing projections to the NAc originate from the ventral tegmental area (VTA) and the prefrontal cortex, and BDNF release activates tropomyosin-related kinase B (TrkB). In this study, we examined the necessity for BDNF-TrkB signaling in the NAc shell during social defeat stress-induced cross-sensitization to amphetamine. Adeno-associated virus expressing short hairpin RNA directed against TrkB (AAV-shTrkB) was infused bilaterally into the NAc shell to knock down TrkB, whereas AAV-GFP (green fluorescent protein) was used as the control virus. Rats were exposed to intermittent social defeat stress or handling procedures; amphetamine challenge was given at 10days after the last defeat and locomotor activity was measured. Stressed rats that received the control virus showed cross-sensitization to amphetamine compared with the handled rats. In contrast, NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization. TrkB knockdown in the NAc was found to reduce the level of phospho-extracellular signal-regulated kinase 1 in this region. NAc TrkB knockdown also prevented stress-induced elevation of BDNF and the glutamate receptor type 1 (GluA1) subunit of AMPA receptor in the VTA, as well as Delta FosB expression in the NAc. These findings indicated that BDNF-TrkB signaling in the NAc shell was required for social defeat stress-induced cross-sensitization. NAc TrkB-BDNF signaling also appeared to be involved in the regulation of GluA1 in the VTA, as well as in the NAc Delta FosB accumulation that could trigger cross-sensitization after social defeat stress.
• Hoffman, A. N., Anouti, D. P., Lacagnina, M. J., Nikulina, E. M., Hammer, R. P., & Conrad, C. D. (2013). Experience-dependent effects of context and restraint stress on corticolimbic c-Fos expression. Stress (Amsterdam, Netherlands), 16(5).
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  Stressors are typically multidimensional, comprised of multiple physical and sensory components that rarely occur as single isolated events. This study used a 2-day stress exposure paradigm to assess functional activation patterns (by Fos expression) in key corticolimbic structures following repeated context, repeated restraint, context followed by restraint or restraint followed by context. On day 1, rats were transported to a novel context and either restrained for 6 h or left undisturbed. On day 2, these two groups were either restrained or not in the same context, then processed for Fos immunohistochemistry. Regardless of prior stress experience, rats exposed to context only on day 2 expressed more Fos-like immunoreactive (IR) labeling in CA1 and CA3 of dorsal hippocampus, basolateral amygdala and central amygdala than those that were not. This pattern was reversed in the dentate gyrus infrapyramidal blade. In contrast, in the infralimbic region of the medial prefrontal cortex (mPFC), the experience of a single restraint on either day 1 or day 2 rats elevated Fos-like IR relative to rats that had been exposed to context alone. These data show that exposure to context produces robust Fos induction in the hippocampus and amygdala, regardless of prior experience with restraint and compared to the immediate experience of restraint, with prior experience modulating Fos expression within the mPFC.
• Wang, J., Bina, R. W., Wingard, J. C., Terwilliger, E. F., Hammer, R. P., & Nikulina, E. M. (2013). Knockdown of tropomyosin-related kinase B receptor expression in the nucleus accumbens shell prevents intermittent social defeat stress-induced cross-sensitization to amphetamine in rats. The European journal of neuroscience.
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  The nucleus accumbens (NAc) is a critical brain region for the rewarding effects of drugs of abuse. Brain-derived neurotrophic factor (BDNF) can facilitate stress- and drug-induced neuroadaptation in the mesocorticolimbic system. BDNF-containing projections to the NAc originate from the ventral tegmental area (VTA) and the prefrontal cortex, and BDNF release activates tropomyosin-related kinase B (TrkB). In this study, we examined the necessity for BDNF-TrkB signaling in the NAc shell during social defeat stress-induced cross-sensitization to amphetamine. Adeno-associated virus expressing short hairpin RNA directed against TrkB (AAV-shTrkB) was infused bilaterally into the NAc shell to knock down TrkB, whereas AAV-GFP (green fluorescent protein) was used as the control virus. Rats were exposed to intermittent social defeat stress or handling procedures; amphetamine challenge was given at 10 days after the last defeat and locomotor activity was measured. Stressed rats that received the control virus showed cross-sensitization to amphetamine compared with the handled rats. In contrast, NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization. TrkB knockdown in the NAc was found to reduce the level of phospho-extracellular signal-regulated kinase 1 in this region. NAc TrkB knockdown also prevented stress-induced elevation of BDNF and the glutamate receptor type 1 (GluA1) subunit of AMPA receptor in the VTA, as well as ΔFosB expression in the NAc. These findings indicated that BDNF-TrkB signaling in the NAc shell was required for social defeat stress-induced cross-sensitization. NAc TrkB-BDNF signaling also appeared to be involved in the regulation of GluA1 in the VTA, as well as in the NAc ΔFosB accumulation that could trigger cross-sensitization after social defeat stress.
• Wang, J., Fanous, S., Terwilliger, E. F., Bass, C. E., Hammer, R. P., & Nikulina, E. M. (2013). BDNF over-expression in the ventral tegmental area prolongs single social defeat stress-induced cross-sensitization to amphetamine and increases deltaFosB expression in mesocorticolimbic regions of rats.. Neuropsychopharmacology, 2286-2296.
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  Social defeat stress induces persistent cross-sensitization to psychostimulants, but the molecular mechanisms underlying the development of cross-sensitization remain unclear. One candidate is brain-derived neurotrophic factor (BDNF). The present research examined whether ventral tegmental area (VTA) BDNF overexpression would prolong the time course of cross-sensitization after a single social defeat stress, which normally produces transient cross-sensitization lasting <1 week. &#916;FosB, a classic molecular marker of addiction, was also measured in mesocorticolimbic terminal regions. Separate groups of intact male Sprague-Dawley rats underwent a single episode of social defeat stress or control handling, followed by amphetamine (AMPH) challenge 3 or 14 days later. AMPH cross-sensitization was apparent 3, but not 14, days after stress. Intra-VTA infusion of adeno-associated viral (AAV-BDNF) vector resulted in a twofold increase of BDNF level in comparison to the group receiving the control virus (AAV-GFP), which lasted at least 45 days. Additionally, overexpression of BDNF in the VTA alone increased &#916;FosB in the nucleus accumbens (NAc) and prefrontal cortex. Fourteen days after viral infusions, a separate group of rats underwent a single social defeat stress or control handling and were challenged with AMPH 14 and 24 days after stress. AAV-BDNF rats exposed to stress showed prolonged cross-sensitization and facilitated sensitization to the second drug challenge. Immunohistochemistry showed that the combination of virally enhanced VTA BDNF, stress, and AMPH resulted in increased &#916;FosB in the NAc shell compared with the other groups. Thus, elevation of VTA BDNF prolongs cross-sensitization, facilitates sensitization, and increases &#916;FosB in mesocorticolimbic terminal regions. As such, elevated VTA BDNF may be a risk factor for drug sensitivity.; doi:10.1038/npp.2013.130
• Nikulina, E. M., Lacagnina, M. J., Fanous, S., Wang, J., & Hammer, R. P. (2012). Intermittent social defeat stress enhances mesocorticolimbic ΔFosB/BDNF co-expression and persistently activates corticotegmental neurons: implication for vulnerability to psychostimulants. Neuroscience, 38-48.
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  (http://www.ncbi.nlm.nih.gov/pubmed/22521816)
• Nikulina, E. M., Lacanina, M. J., Fanous, S., Wang, J., & Hammer, R. P. (2012). Intermittent social defeat stress enhances mesocorticolimbic BDNF -FosB co-expression and persistently activates corticotegmental neurons: Implication for vulnerability to psychostimulants. Neuroscience, 38-48.
• Nikulina, E. M., Lacanina, M. J., Fanous, S., Wang, J., & Hammer, R. P. (2012). Intermittent social defeat stress enhances mesocorticolimbic BDNF-FosB co-expression and persistently activates corticotegmental neurons: Implication for vulnerability to psychostimulants. Neuroscience, 38-48.
• Nikulina, E. M., Wang, J., Kleiman, J., Terwilliger, E. F., Bass, C., & Hammer, R. P. (2012). Knockdown of TrkB in the rat nucleus accumbens alters BDNF signaling in the mesocorticolimbic circuit and prevents effects of social defeat stress on amphetamine cross-sensitization. Neuropsychopharmacology, S1(38), S122.
• Parga, A., & Hammer, R. P. (2012). Auditory cortical activation after dopamine infusion in caudal caudatoputamen of the rat. Biol. Psychiatry, 312S.
• Berger, A. K., Green, T., Seigel, S. J., Nestler, E. J., & Hammer, R. P. (2011). CREB phosphorylation in nucleus accumbens underlies sustained recovery of sensorimotor gating following repeated D2-like receptor agonist treatment in rats. Biol. Psychiatry, 288-294.
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  (http://www.ncbi.nlm.nih.gov/pubmed/21035786)
• Berger, A. K., Green, T., Siegel, S. J., Nestler, E. J., & Hammer, R. P. (2011). cAMP response element binding protein phosphorylation in nucleus accumbens underlies sustained recovery of sensorimotor gating following repeated D₂-like receptor agonist treatment in rats. Biological psychiatry, 69(3).
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  Prepulse inhibition (PPI) is a cross-species measure of sensorimotor gating. PPI deficits are observed in humans and rats upon acute treatment with dopamine D₂-like receptor agonists and in patients with schizophrenia. Repeated treatment with a D₂-like agonist, however, reverses PPI deficits and increases cyclic adenosine monophosphate (cAMP) signaling in the nucleus accumbens (NAc). This study examined the short- and long-term effects on PPI of treatment with quinpirole and ropinirole, dopamine D₂/D₃ receptor agonists, and the molecular mechanism by which they occur.
• Fanous, S., Lacagnina, M. J., Nikulina, E. M., & Hammer, R. P. (2011). Sensitized activation of Fos and brain-derived neurotrophic factor in the medial prefrontal cortex and ventral tegmental area accompanies behavioral sensitization to amphetamine. Neuropharmacology, 61(4).
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  Behavioral sensitization, or augmented locomotor response to successive drug exposures, results from neuroadaptive changes contributing to addiction. Both the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA) influence behavioral sensitization and display increased immediate-early gene and BDNF expression after psychostimulant administration. Here we investigate whether mPFC neurons innervating the VTA exhibit altered Fos or BDNF expression during long-term sensitization to amphetamine. Male Sprague-Dawley rats underwent unilateral intra-VTA infusion of the retrograde tracer Fluorogold (FG), followed by 5 daily injections of either amphetamine (2.5 mg/kg, i.p.) or saline vehicle. Four weeks later, rats were challenged with amphetamine (1.0 mg/kg, i.p.) or saline (1.0 mL/kg, i.p.). Repeated amphetamine treatment produced locomotor sensitization upon drug challenge. Two hours later, rats were euthanized, and mPFC sections were double-immunolabeled for either Fos-FG or Fos-BDNF. Tissue from the VTA was also double-immunolabeled for Fos-BDNF. Amphetamine challenge increased Fos and BDNF expression in the mPFC regardless of prior drug experience, and further augmented mPFC BDNF expression in sensitized rats. Similarly, more Fos-FG and Fos-BDNF double-labeling was observed in the mPFC of sensitized rats compared to drug-naïve rats after amphetamine challenge. Repeated amphetamine treatment also increased VTA BDNF, while both acute and repeated amphetamine treatment increased Fos and Fos-BDNF co-labeling, an effect enhanced in sensitized rats. These findings point to a role of cortico-tegmental BDNF in long-term amphetamine sensitization.
• Fanous, S., Terwilliger, E. F., Hammer, R. P., & Nikulina, E. M. (2011). Viral depletion of VTA BDNF in rats modulates social behavior, consequences of intermittent social defeat stress, and long-term weight regulation. Neuroscience letters, 502(3).
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  Mesolimbic brain-derived neurotrophic factor (BDNF) is implicated in sustained behavioral changes following chronic social stress, and its depletion may reduce susceptibility to such behavioral alterations. Enhanced mesolimbic BDNF is proposed as pro-depressive and anhedonic, while depleting ventral tegmetal area (VTA) BDNF increases weight by enhancing hedonic eating. Here, we questioned whether depletion of VTA BDNF would alleviate social defeat stress-induced deficits in weight regulation, or affect social behavior in the presence or absence of social stress. Male Sprague-Dawley rats received bilateral intra-VTA infusions of adeno-associated virus (AAV) vectors containing shRNA against BDNF or a control virus. Three weeks later, rats underwent 4 episodes of social defeat stress involving exposure to an aggressive Long-Evans resident rat, or control handling every third day. Depleted VTA BDNF conferred resistance to the deficient weight regulation normally observed during intermittent social defeat stress, and enhanced long-term weight gain regardless of stress history. In addition, social approach and avoidance behavior towards a novel social target were measured 7 weeks after stress. Social defeat stress chronically reduced social behavior, whereas depletion of VTA BDNF chronically increased social behavior. Our results reveal that depletion of VTA BDNF alleviates some consequences of intermittent social defeat stress, enhances social behavior, and may contribute to weight gain. These data implicate VTA BDNF in protracted behavioral responses to stress, social stimuli, and weight regulation.
• Fanous, S., Hammer, R. P., & Nikulina, E. M. (2010). Short- and long-term effects of intermittent social defeat stress on BDNF expression in mesocorticolimbic brain regions. Neuroscience, 598-607.
• Fanous, S., Hammer, R. P., & Nikulina, E. M. (2010). Short- and long-term effects of intermittent subordination stress on brain-derived neurotrophic factor expression in mesocorticolimbic brain regions. Neuroscience, 598-607.
• Leussis, M. P., Frayne, M., Saito, M., Berry, E., Aldinger, K. A., Rockwell, G. N., Hammer, R. P., Baskin-Hill, A. E., Singer, J., Nadeau, J., Sklar, P., & Petryshen, T. L. (2009). Genomic survey of prepulse inhibition in mouse B6.A chromosome substitution strains. Genes, Brain and Behavior, 806-816.
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  (http://www.ncbi.nlm.nih.gov/pubmed/19694817)
• Hammer, L. M., Nikulina, E. M., Arrillaga-Romany, I., Miczek, K. A., & Hammer, L. M. (2008). Long-lasting alteration in mesocorticolimbic structures after repeated social defeat stress in rats: time course of mu-opioid receptor mRNA and FosB/DeltaFosB immunoreactivity. The European journal of neuroscience, 27(9).
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  Social defeat stress is a salient stressor that induces neuroadaptive changes in the mesocorticolimbic dopaminergic system. Substantial evidence indicates that mu-opioid receptors (MORs) modulate dopamine transmission in the ventral tegmental area (VTA). FosB/DeltaFosB protein accumulation in dopaminergic projections during repeated treatments is thought to be involved in long-term neuroplasticity. In this study we characterize the magnitude and time-course of MOR mRNA expression and FosB/DeltaFosB immunoreactivity in mesocorticolimbic regions following repeated social defeat stress. Effects of brief repeated social defeat stress or control handling procedures were studied in rats either 2 h after the last exposure, or 3, 7, 14, 21 and 28 days later. We found that MOR mRNA expression in the VTA doubled after the last stress compared with handling, and remained 30-70% higher until day 21. The number of FosB/DeltaFosB-labeled neurons in regions of the frontal cortex, nucleus accumbens (NAc) shell and core, and in the medial, central and basolateral amygdala increased significantly immediately after the last stress episode, and remained enhanced for 21 days. Another group of rats received bilateral intra-VTA infusion of the MOR agonist, DAMGO, 7 days after the last stress. Prior social defeat stress augmented DAMGO-induced Fos expression in the NAc shell, suggesting that Fos expression in this region might be the direct result of MOR activity in the VTA. Social defeat stress leads to an increased capacity for MOR activation in the VTA, which may be relevant to enduring FosB/DeltaFosB expression in mesocorticolimbic areas and to the behaviorally sensitized response to psychostimulant drugs.
• Nikulina, E. M., Arrillaga-Romany, I., Hammer, R. P., & Miczek, K. A. (2008). Long-lasting functional activation in mesolimbic structures after repeated social defeat stress: time course of µ-opioid mRNA and FosB immunoreactivity. European Journal of Neuroscience, 2272-2284.
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  (http://www.ncbi.nlm.nih.gov/pubmed/18445218)
• Chung, J. D., Krupin, A. S., Grundt, P., Newman, A. H., & Hammer, R. P. (2006). Recovery of sensorimotor gating is blocked by selective D3-receptor antagonist pretreatment in rats. Biological Psychiatry, 89S.
• Swerdlow, N. R., Krupin, A. S., Bongiovanni, M. J., Shoemaker, J. M., Goins, J. C., & Hammer, R. P. (2006). Heritable differences in the dopaminergic regulation of behavior in rats: relationship to D2-like receptor G-protein function. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 31(4).
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  We reported heritable differences between Sprague-Dawley (SD) and Long Evans (LE) rats in their sensitivity to the disruption of prepulse inhibition of startle (PPI) by dopamine (DA) agonists, and in their basal levels and turnover of forebrain DA. In an effort to better understand these differences, we assessed strain patterns in the efficacy of D2-like receptor-G-protein coupling using [35S]GTPgammaS binding in brain regions that contribute to the dopaminergic regulation of PPI. Sensitivity to the PPI-disruptive effects of apomorphine (APO) was examined in SD, LE, and F1 (SD x LE) rats. Basal and DA-stimulated [35S]GTPgammaS binding were then assessed in these rats using conditions that preferentially exclude Gs proteins to favor visualization of D2-like receptors. To explore the behavioral specificity of these strain differences, locomotor responses to APO and amphetamine (AMPH) were also assessed in SD, LE, and F1 rats. Strain differences were evident in the PPI-disruptive effects of APO (SD>F1>LE), and in the locomotor responses to AMPH (LE>F1>SD) and APO (SD exhibited motor suppression, LE exhibited motor activation). Compared to SD rats, LE rats exhibited greater DA-stimulated [35S]GTPgammaS binding in nucleus accumbens and caudatoputamen, while F1 progeny had intermediate levels. In conclusion, SD and LE rats exhibit heritable differences in D2-mediated behavioral and biochemical measures. Conceivably, genes that regulate heritable differences in forebrain D2 function may contribute to heritable differences in PPI in patients with specific neuropsychiatric disorders, including schizophrenia and Tourette Syndrome.
• Arrillaga-Romany, I. C., & Hammer, R. P. (2005). Corticotropin-releasing factor (CRF) impairs sensorimotor gating in the Sprague-Dawley rat: reversal by clozapine and raclopride. Neuropsychopharmacology, S114.
• Covington, H. E., Kikusui, T., Goodhue, J., Nikulina, E. M., Hammer, R. P., & Miczek, K. A. (2005). Brief social defeat stress: long lasting effects on cocaine taking during a binge and zif268 mRNA expression in the amygdala and prefrontal cortex. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 30(2).
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  Social stress can engender behavioral and neural sensitization and this process appears to enhance the transition to compulsive drug abuse. Exposures to brief social defeat stress in rats have significant consequences on cocaine-reinforced behavior and on the level of functional activation within regions of the mesocorticolimbic dopamine system. The objectives of the current study were to examine the enduring consequences of brief episodes of social defeat stress on cocaine bingeing (during 24 h of continuous access) and on the emergence of neural adaptations as revealed by zif268 immediate early gene expression. Adult, male Long-Evans rats were subjected to four 25 min episodes of social defeat (once every 72 h). After 2 months, cocaine binges or zif268 mRNA gene expression were studied after confirming behavioral cross-sensitization to stimulant challenge. Sensitization to social defeat increased cocaine intake during a 24 h binge, effectively abolishing the typical circadian pattern of intake. Furthermore, 60 days after exposure to the sensitizing regimen of social defeat, levels of functional activation, measured by zif268 mRNA expression, in the central and medial amygdala were increased, while levels of activation in the medial prefrontal cortex were decreased. Persistent stress-induced levels of zif268 in the central and medial amygdala were attenuated by an injection of amphetamine (1.0 mg/kg). Divergent changes in zif268 within the amygdala and cortex 2 months after social defeat stress indicate the vulnerability of distinct cellular populations in networks that modulate the behavioral actions of psychomotor stimulants.
• Hammer, R. P., & Krupin, A. S. (2005). Repeated ropinirole treatment reverses sensorimotor gating deficits in rats. Biological Psychiatry, 21S.
• Hammer, R. P., Arrillaga-Romany, I. C., & Windsor, A. M. (2005). Is dopamine to blame for CRF-induced sensorimotor gating deficits in rats?, in ACNP Panel entitled: Animal models of deficient sensorimotor gating: A new role for the corticotropin-releasing factor system?. Neuropsychopharmacology, S44.
• Hammer, R. P., Krupin, A. S., & Seigel, S. J. (2005). Surgically-implantable long-term quinpirole delivery reverses sensorimotor gating deficits in rats. Biological Psychiatry, 21S.
• Nikulina, E. M., Miczek, K. A., & Hammer, R. P. (2005). Prolonged effects of repeated social defeat stress on mRNA expression and function of mu-opioid receptors in the ventral tegmental area of rats. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 30(6).
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  Social defeat stress alters the activity of mesocorticolimbic dopamine projections from the ventral tegmental area (VTA), a process that has been implicated in the development of sensitization and drug-seeking behavior. We showed previously that acute brief social defeat stress increased short-term expression of mu-opioid receptor mRNA in the VTA. The present study assessed the presence and functional significance of mu-opioid receptor mRNA expression 1 week after the last episode of social defeat stress. Social defeat stress was induced in intruder rats during short confrontations with an aggressive resident rat, and subsequent exposures behind a protective screen once a day for 5 days. Regional mu-receptor mRNA levels were assessed by in situ hybridization histochemistry, and the amount of mRNA labeling was measured in the VTA and the substantia nigra (SN). Expression of mu-opioid receptor mRNA was significantly higher in defeated rats relative to handled control animals in the VTA, but not in the SN. In an additional group of rats, bilateral local intra-VTA injection of the selective mu-opioid receptor agonist DAMGO (1.0 microg per side) was performed 7-10 days after the last defeat stress or handling control procedure. Baseline motor activity did not differ between control and stressed rats. Intra-VTA DAMGO significantly increased locomotor activity in stressed rats compared to handled control rats. These results suggest that repeated social stress upregulates VTA mu-opioid receptors and can produce locomotor activation via stimulation of these receptors. This locomotor effect is probably the consequence of enhanced disinhibition of mesolimbic dopamine neurons.
• Petryshen, T. L., Kirby, A., Hammer, R. P., Purcell, S., O'Leary, S. B., Singer, J. B., Hill, A. E., Nadeau, J. H., Daly, M. J., & Sklar, P. (2005). Two quantitative trait loci for prepulse inhibition of startle identified on mouse chromosome 16 using chromosome substitution strains. Genetics, 171(4).
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  Prepulse inhibition (PPI) of acoustic startle is a genetically complex quantitative phenotype of considerable medical interest due to its impairment in psychiatric disorders such as schizophrenia. To identify quantitative trait loci (QTL) involved in mouse PPI, we studied mouse chromosome substitution strains (CSS) that each carry a homologous chromosome pair from the A/J inbred strain on a host C57BL/6J inbred strain background. We determined that the chromosome 16 substitution strain has elevated PPI compared to C57BL/6J (P = 1.6 x 10(-11)), indicating that chromosome 16 carries one or more PPI genes. QTL mapping using 87 F(2) intercross progeny identified two significant chromosome 16 loci with LODs of 3.9 and 4.7 (significance threshold LOD is 2.3). The QTL were each highly significant independently and do not appear to interact. Sequence variation between B6 and A/J was used to identify strong candidate genes in the QTL regions, some of which have known neuronal functions. In conclusion, we used mouse CSS to rapidly and efficiently identify two significant QTL for PPI on mouse chromosome 16. The regions contain a limited number of strong biological candidate genes that are potential risk genes for psychiatric disorders in which patients have PPI impairments.
• Culm, K. E., & Hammer, R. P. (2004). Recovery of sensorimotor gating without G protein adaptation after repeated D2-like dopamine receptor agonist treatment in rats. The Journal of pharmacology and experimental therapeutics, 308(2).
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  Sensorimotor gating, a neural process severely disrupted in patients with schizophrenia, can be measured by assessing prepulse inhibition (PPI) of acoustic startle responses. PPI is disrupted in experimental animals by stimulation of D(2)-like dopamine receptors in the nucleus accumbens (NAc). We examined the effect of repeated treatment with a selective dopamine D(2)-like receptor agonist, quinpirole, and characterized the molecular substrates of the resulting PPI adaptation. Animals were treated once daily for 10 or 28 consecutive days with quinpirole (0.0, 0.05, 0.1, or 0.3 mg/kg, s.c.), and the effect on PPI was assessed throughout the treatment period. PPI was reduced after acute quinpirole administration, but gradually increased with repeated treatment. Quinpirole-induced PPI disruption was attenuated after 10 days of treatment at lower doses, but complete recovery was not apparent until the treatment period was extended to 28 days. Since chronic drug exposure can alter the dopamine system, we sought to characterize the effects of repeated quinpirole treatment on G proteins coupled to D(2)-like receptors in the NAc. Guanosine 5'-O-(3-[(35)S]thiotriphosphate) ([(35)S]GTPgammaS) binding and Western blot analysis revealed that repeated quinpirole treatment had no effect on NAc D(2)-like receptor G protein function or G protein levels. These data indicate that repeated activation of D(2)-like receptors by quinpirole produces tolerance in the absence of receptor or G protein changes, suggesting that the locus of dopaminergic adaptation might be at the intracellular level.
• Culm, K. E., Lugo-Escobar, N., Hope, B. T., & Hammer, R. P. (2004). Repeated quinpirole treatment increases cAMP-dependent protein kinase activity and CREB phosphorylation in nucleus accumbens and reverses quinpirole-induced sensorimotor gating deficits in rats. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 29(10).
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  Sensorimotor gating, which is severely disrupted in schizophrenic patients, can be measured by assessing prepulse inhibition of the acoustic startle response (PPI). Acute administration of D2-like receptor agonists such as quinpirole reduces PPI, but tolerance occurs upon repeated administration. In the present study, PPI in rats was reduced by acute quinpirole (0.1 mg/kg, s.c.), but not following repeated quinpirole treatment once daily for 28 days. Repeated quinpirole treatment did not alter the levels of basal-, forskolin- (5 microM), or SKF 82958- (10 microM) stimulated adenylate cyclase activity in the nucleus accumbens (NAc), but significantly increased cAMP-dependent protein kinase (PKA) activity. Phosphorylation of cAMP response element-binding protein (CREB) was significantly greater in the NAc after repeated quinpirole treatment than after repeated saline treatment with or without acute quinpirole challenge. Activation of PKA by intra-accumbens infusion of the cAMP analog, Sp-cAMPS, prevented acute quinpirole-induced PPI disruption, similar to the behavioral effect observed following repeated quinpirole treatment. Thus, repeated quinpirole treatment increases NAc PKA activity and CREB phosphorylation, and this neuroadaptive response might facilitate the recovery of sensorimotor gating in schizophrenia.
• Krupin, A. S., & Hammer, R. P. (2004). Ropinirole and sensorimotor gating. Biological Psychiatry, 8(55), 48S.
• Miczek, K. A., Covington, H. E., Nikulina, E. M., & Hammer, R. P. (2004). Aggression and defeat: persistent effects on cocaine self-administration and gene expression in peptidergic and aminergic mesocorticolimbic circuits. Neuroscience and biobehavioral reviews, 27(8).
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  The question of how ostensibly aversive social stress experiences in an aggressive confrontation can persistently increase intense drug taking such as cocaine 'bingeing' needs to be resolved. The biology of social conflict highlights distinctive behavioral, cardiovascular and endocrine profiles of dominant and subordinate animals, as seen also in rodents and primates under laboratory conditions. In contrast to continuous subordination stress that produces chronic pathophysiological consequences and often is fatal, animals adapt to brief episodes of social defeat stress, but show enduring functional activation in mesocorticolimbic microcircuits. Uncontrollable episodes of social defeat stress produce long-lasting tolerance to opiate analgesia and, concurrently, behavioral sensitization to challenges with either amphetamine or cocaine. One week after a single social defeat stress, cross-sensitization to cocaine is evident in terms of enhanced motor activity as well as in terms of increased Fos labeling in the periaqueductal grey area, the locus coeruleus, and the dorsal raphe nuclei. When challenged with a low amphetamine dose, the behavioral and neural effects of repeated brief episodes of social defeat stress persist for months. Previous exposure to social defeat stress can (1). significantly shorten the latency to acquire cocaine self-administration, (2). maintain this behavior at low cocaine unit doses, (3). significantly increase the levels of cocaine taking during a 24 h binge of continuous drug availability, (4). dysregulate the timing of consecutive infusions, and (5). abolish the circadian pattern of self-administration. Amygdaloid modulation, especially originating from central and basolateral nuclei, of dopaminergic pathways via peptidergic and glutamatergic neurons appears to be a key mechanism by which social defeat stress affects cocaine self-administration. Social stress alters the feedback from prefrontal cortex and thereby may contribute to the dysregulation of dopaminergic activity that is necessary for cocaine self-administration.
• Nikulina, E. M., Covington, H. E., Ganschow, L., Hammer, R. P., & Miczek, K. A. (2004). Long-term behavioral and neuronal cross-sensitization to amphetamine induced by repeated brief social defeat stress: Fos in the ventral tegmental area and amygdala. Neuroscience, 4(123), 857-865.
• Nikulina, E. M., Covington, H. E., Goodhue, J., Ganschow, L., Hammer, R. P., & Miczek, K. A. (2004). Long-term behavioral and neuronal cross-sensitization to amphetamine induced by repeated brief social defeat stress: Fos in the ventral tegmental area and amygdala. Neuroscience, 857-865.
• Nikulina, E. M., Miczek, K. A., & Hammer, R. P. (2004). Prolonged changes in ventral tegmental area neurons after repeated social defeat stress in rats. Behavioral Pharmacology, A22.
• Robinson, D. A., O'Brien, P. K., Gheewala, R. M., Nikulina, E. M., Payne, D. D., Hammer, R. P., & Warner, K. G. (2004). Differential expression of neuronal fos protein after cold water drowning and controlled rewarming. Journal of the American College of Surgeons, 198(3).
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  Cardiopulmonary bypass has often been applied to revive victims of cold water drowning. The success of resuscitative efforts in patients who have sustained severe hypothermia is largely determined by neurologic outcomes. Measurement of Fos, the protein product of the immediate-early gene c-fos, is a marker of cerebral injury.
• Culm, K. E., Lim, A. M., Onton, J. A., & Hammer, R. P. (2003). Reduced G(i) and G(o) protein function in the rat nucleus accumbens attenuates sensorimotor gating deficits. Brain research, 982(1).
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  Prepulse inhibition of the acoustic startle response (PPI) is a cross-species measure of sensorimotor gating, which is severely disrupted in patients with schizophrenia. PPI deficits can be produced in experimental animals by administration of selective D(2)-like dopamine receptor agonists in the nucleus accumbens (NAc). G proteins coupled to these receptors reportedly are altered in the NAc of patients with schizophrenia. Therefore, we sought to determine whether experimental inactivation of intracellular G proteins in the NAc alters PPI. In adult male Sprague-Dawley rats, baseline PPI was determined by presenting acoustic pulse stimuli (120 dB) alone or preceded 100 ms earlier by prepulse stimuli (3, 6 or 12 dB above 70 dB ambient noise). PPI disruption was assessed in the presence of quinpirole (0.0, 0.05, 0.1, 0.5 mg/kg, sc), and pertussis toxin (PTX; 0.05 microg/side) was then infused into the NAc bilaterally. Ten days later, quinpirole-mediated disruption of PPI was significantly reduced; neither PTX alone, nor heat-inactivated PTX had any effect on quinpirole-induced PPI reductions. PPI was significantly higher after PTX infusion upon moderate quinpirole challenge, suggesting that D(2)-like receptors were less effective. PTX treatment significantly reduced basal and dopamine-stimulated [35S]GTPgammaS binding in the NAc core and shell, and reduced G(i)(alpha) protein immunoreactivity in the NAc. The results suggest that PPI disruption mediated by D(2)-like receptor activation in the NAc depends on coupling to G(i) and G(o) proteins, alteration of which could cause sensorimotor gating deficits in schizophrenia.
• Nikulina, E. M., Culm, K. E., & Hammer, R. P. (2002). Prolonged impairment of prepulse inhibition by repeated social stress in rats. Biological Psychiatry, 22S.
• Nikulina, E. M., Miczek, K. A., & Hammer, R. P. (2001). Repeated social stress sensitizes Fos response to amphetamine in mesocorticolimbic dopamine regions of the rat brain. Biological Psychiatry, 120S.
• Byrnes, J. J., & Hammer, R. P. (2000). The disruptive effect of cocaine on prepulse inhibition is prevented by repeated administration in rats. Neuropsychopharmacology, 551-554.
• Byrnes, J. J., Pantke, M. M., Onton, J., & Hammer, R. P. (2000). Inhibition of nitric oxide synthase in the ventral tegmental area attenuates cocaine-mediated motor behavior in rats. Prog. Neuro.-Psychopharmacol. Biol. Psych., 261-273.
• Culm, K. E., Chen, J. F., Schwarzschild, M. A., & Hammer, R. P. (2000). Adenosine A2A receptor knockout prevents disruption of prepulse inhibition by acute cocaine. FASEB Journal, 1320.
• Culm, K. E., Link, T., & Hammer, R. P. (2000). Sustained attenuation of apomorphine-induced disruption of prepulse inhibition following chronic haloperidol treatment in rats. Society for Neuroscience Abstracts, 2272.
• Faccidomo, S., Collins, L., Ahmed, R., Hammer, R. P., Hood, K. E., & Miczek, K. A. (2000). Miczek: Serotonin transporter binding density in male mice bred for high and low levels of aggression. Society for Neuroscience Abstracts, 1767.
• Gulledge, C. C., Mann, P., Bridges, R. S., Bialos, M., & Hammer, R. P. (2000). Expression of µ-opioid receptor mRNA in the medial preoptic area of juvenile rats. Developmental Brain Research, 269-276.
• Mutschler, N. H., Miczek, K. A., & Hammer, R. P. (2000). Prolonged reduction of zif268 messenger RNA expression during withdrawal following cocaine self-administration. Neuroscience, 531-538.
• Nikulina, E. M., Culm, K., Covington, H., Miczek, K. A., & Hammer, R. P. (2000). Cross-sensitization to amphetamine induced by repeated social stress: Fos expression. Society for Neuroscience Abstracts, 1759.
• Nikulina, E. M., Miczek, K. A., & Hammer, R. P. (2000). Repeated social stress induces prolonged Fos expression in limbic cortex. Biological Psychiatry, 77S.
• Onton, J., & Hammer, R. P. (2000). Behavioral sensitization is associated with reduced zif268 mRNA expression in the nucleus accumbens during withdrawal following cocaine self-administration. Society for Neuroscience Abstracts, 526.

Presentations

• Hoit, J. D., & Hammer, R. P. (2017, February). Building productive and ethical mentoring relationships. Workshop for the University of Arizona Office for the Responsible Conduct of Research (RCR). Tucson, AZ: University of Arizona Office for the Responsible Conduct of Research (RCR).
• Maple, A. M., Meyers, K. T., Walker, D. M., Cahill, M. E., Gallitano, A. M., Nikulina, E. M., Nestler, E. J., & Hammer, R. P. (2016, May). Ropinirole Treatment Resulting in Recovery of Sensorimotor Gating Induces ΔFosB in Mouse Nucleus Accumbens Neurons that Co-express D1 and D3 Dopamine Receptors. Society of Biological Psychiatry Annual Meeting. Atlanta: Society of Biological Psychiatry Annual Meeting.
• Nikulina, E. M., Johnston, C. E., & Hammer, R. P. (2015, June). Localization of phosphoAKT in VTA GABA neurons after social stress exposure. International Behavioral Neuroscience Society.

Poster Presentations

• Hammer, R. P., Nikulina, E. M., Zafar, T. J., Yellowman, Z., & Yang, R. (2021, November). Optogenetic Inhibition of Posterior Caudatoputamen Indirect Pathway Neurons Causes Auditory Cortical Activation in Rats. Society for Neuroscience Annual Meeting. Virtual: Society for Neuroscience.
• Zafar, T. J., Yellowman, Z., Nikulina, E. M., & Hammer, R. P. (2021, November). Haloperidol pretreatment reduces auditory cortex Fos expression caused by posterior striatal dopamine infusion in proestrus female rats. Society for Neuroscience Annual Meeting. virtual: Society for Neuroscience.
• Nikulina, E. M., Rudolph, M., Azuma, A., Zafar, T., & Hammer, R. P. (2019, 05-02-2019). Sex-dependent effect of social defeat stress for amphetamine cross-sensitization: functional role of AMPA GluA1 subunit of glutamate receptors expression in the ventral tegmental area. ABRC Research Conference. BSPB: ABRC.
• Rudolph, M. L., Azuma, A. F., Neve, R. L., Hammer, R. P., & Nikulina, E. M. (2019, November). Mesolimbic dynamics underlying estrous cycle-dependent differences in social stress-induced amphetamine cross-sensitization in female rats. 2019 Society for Neuroscience Annual Meeting. Chicago, IL: Society for Neuroscience.
• Zafar, T. J., Yellowman, Z., Nikulina, E. M., & Hammer, R. P. (2019, November). Posterior striatal dopamine infusion increases striatal and auditory cortical Fos expression to a greater extent in proestrus than in metestrus female rats. Society for Neuroscience Annual Meeting. Chicago, IL.
• Meyers, K. T., Maple, A. M., Walker, D. M., Cahill, M. E., Gallitano, A. M., Nikulina, E. M., Nestler, E. J., & Hammer, R. P. (2016, November). Repeated ropinirole treatment resulting in recovery of sensorimotor gating induces ΔFosB in mouse nucleus accumbens neurons that co-express D1 and D3 dopamine receptors, but not D2 receptors. Society for Neuroscience Annual Meeting. San Diego, CA: Society for Neuroscience.
• Hakes, E. B., Munoz, G. A., Bass, C. E., Nikulina, E. M., & Hammer, R. P. (2015, May). BDNF knockdown in the VTA blocks social stress-induced deficits in social behavior and nucleus accumbens ΔFosB expression. Society of Biological Psychiatry Annual Meeting. Toronto, Ontario, Canada: Society of Biological Psychiatry.
• Johnston, C. E., Hammer, R. P., & Nikulina, E. M. (2015, November). Inhibition of AKT phosphorylation in the rat ventral tegmental area prevents intermittent social defeat stress-induced weight gain deficits and the expression of amphetamine cross-sensitization. Society for Neuroscience Annual Meeting. Chicago, IL: Society for Neuroscience.
• Nikulina, E. M., Johnston, C. E., & Hammer, R. P. (2015, August). Localization of phosphoAKT in VTA GABA neurons after social stress exposure. European Behavioral Pharmacology Society Annual Meeting.
• Parga, A., Munoz, G., & Hammer, R. P. (2015, May). Excessive Striatal Dopamine Activates Auditory Cortex Via Striato-Pallido-Thalamo-Cortical Projections in the Rat. Society of Biological Psychiatry Annual Meeting. Toronto, Ontario, Canada: Society of Biological Psychiatry.

Others

• Hoffman, A. N., Parga, A., Lorson, N. G., Paode, P., Watterson, L., Nikulina, E. M., Hammer, R. P., & Conrad, C. D. (2013, Spring). Chronic stress-induced enhanced fear memories are resistant to reconsolidation in an animal model of post-traumatic stress disorder. 2013 Neuroscience Meeting Planner.
• Johnston, C. E., Herschel, D., Lasek, A. W., Hammer, R. P., & Nikulina, E. M. (2013, Spring). Intermittent social defeat stress increases GABAergic AKT phosphorylation in the ventral tegmental area downstream of mu-opioid receptor upregulation. 2013 Neuroscience Meeting Planner.
• Maple, A. M., Call, T., Vialou, V. F., Nestler, E. J., Nikulina, E. M., & Hammer, R. P. (2013, Spring). DeltaFosB in nucleus accumbens underlies recovery of sensorimotor gating following repeated D2- like agonist treatment in rats. 2013 Neuroscience Meeting Planner.
• Nikulina, E. M., Herschel, D., Johnston, C. E., & Hammer, R. P. (2013, Spring). The impact of social buffering on the behavioral consequences of intermittent social defeat stress and ΔFosB expression in mesocorticolimbic regions of rats. 2013 Neuroscience Meeting Planner.
• Nikulina, E. M., Wang, J., & Hammer, R. P. (2013, Spring). Social stress-induced sensitization to psychostimulants: essential role of BDNF signaling in mesocorticolimbic circuits. European Behavioral Pharmacology Society Abstracts.
• Parga, A., & Hammer, R. P. (2013, Spring). Attenuation of striatal dopamine-induced auditory cortical activation by D1 or D2 receptor-selective antagonists in the rat. Biol. Psychiatry.
• Parga, A., Lavarnway, V., Nikulina, E. M., & Hammer, R. P. (2013, Spring). Trans-synaptic retrograde tracing of an auditory cortical circuit from posterior caudatoputamen in the rat. 2013 Neuroscience Meeting Planner.
• Thomas, T. C., Ray-Jones, H., Hammer, R. P., Adelson, P. D., & Lifshitz, J. (2013, Spring). Diffuse brain injury results in morphological changes to neurons that parallel development of late-onset morbidity in rats. 2013 Neuroscience Meeting Planner.
• Thomas, T. C., Ray-Jones, H., Hammer, R. P., Adelson, P. D., & Lifshitz, J. (2013, Spring). Morphological changes in neurons along a diffuse-injured circuit associated with the development of late-onset morbidity in rats. J. Neurotrauma.
• Wang, J., Bastle, R., Bass, C. E., Hammer, R. P., Neisewander, J., & Nikulina, E. M. (2013, Spring). BDNF over-expression in the ventral tegmental area potentiates intermittent social defeat stress-induced escalation of cocaine self-administration. 2013 Neuroscience Meeting Planner.
• Anouti, D. P., Hoffman, A. N., Lacagnina, M. J., Krigbaum, A., Lorson, N., Campbell, A. N., Nikulina, E. M., Hammer, R. P., & Conrad, C. D. (2012, Spring). Functional Activation Patterns of Forebrain Structures and Corticosterone Levels: Are they experience-dependent following a prior exposure to restraint stress?. 2012 SOLUR Undergraduate Research Symposium.
• Johnston, C. E., Lasek, A. W., Heberlein, U., Hammer, R. P., & Nikulina, E. M. (2012, Spring). Knockdown of mu-opioid receptors in the ventral tegmental area: Critical effect on BDNF expression after intermittent social defeat stress. 2012 Neuroscience Meeting Planner.
• Maple, A. M., Nikulina, E. M., & Hammer, R. P. (2012, Spring). Repeated quinpirole treatment reverses suppression of conditioned avoidance responding and induces ΔFosB in the rat nucleus accumbens. 2012 Neuroscience Meeting Planner.
• Wang, J., Bastle, R. M., Terwilliger, E. F., Neisewander, J. L., Hammer, R. P., & Nikulina, E. M. (2012, Spring). BDNF overexpression in ventral tegmental area: escalation of cocaine self-administration and elevated ΔFosB expression in rat nucleus accumbens. 2012 Neuroscience Meeting Planner.
• Anouti, D. P., Hoffman, A. N., Nikulina, E. M., Hammer, R. P., & Conrad, C. D. (2011, Spring). Patterns of functional brain activation using c-fos in response to a single and repeated exposure to restraint stress. 2011 HHMI-SOLUR Symposium.
• Bastle, R. M., Dickey, E. D., Hammer, R. P., & Neisewander, J. L. (2011, Spring). Region-specific changes in zif268 mRNA following cocaine self-administration, abstinence and extinction training. College of Problems on Drug Dependence.
• Britton, M. J., Maple, A. M., Nikulina, E. M., & Hammer, R. P. (2011, Spring). Effect of repeated aripiprazole treatment on prepulse inhibition and alleviation of quinpirole-induced sensorimotor gating deficits in rats. 2011 HHMI-SOLUR Symposium.
• Chang, W. L., Saint Marie, R. L., Breier, M. R., Yang, A., Mizera, M., Hammer, R. P., & Swerdlow, N. R. (2011, Spring). Signaling Pathways of the D3 agonist pramipexole in the rat ventral forebrain. 2011 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience.
• Hoffman, A. N., Anouti, D. P., Lacagnina, M. J., Nikulina, E. M., & Hammer, R. P. (2011, Spring). unctional activation of limbic structures after a single and second exposure to restraint stress. 2011 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience.
• Johnston, C. E., Lasek, A. W., Heberlein, U., Hammer, R. P., & Nikulina, E. M. (2011, Spring). Knockdown of ventral tegmental area mu-opioid receptor by shRNA prevents social defeat stress-induced cross-sensitization to amphetamine in rats. 2011 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience.
• Lacagnina, M. J., Terwilliger, E. F., Hammer, R. P., & Nikulina, E. M. (2011, Spring). Viral-mediated knockdown of BDNF in the dorsal medial prefrontal cortex is sufficient to prevent social defeat stress-induced amphetamine cross-sensitization in rats. 2011 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience.
• Nikulina, E. M., Lacagnina, M. J., Wang, J., Terwilliger, E. F., & Hammer, R. P. (2011, Spring). BDNF in prefrontal cortex and ventral tegmental area: social defeat stress-induced cross-sensitization and deltaFosB expression in nucleus accumbens. European Behavioral Pharmacology Society Abstracts.
• Parga, A., Kayir, H., Markou, A., & Hammer, R. P. (2011, Spring). Effects of repeated PCP and chronic clozapine treatment on regional brain zif268 expression. 2011 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience.
• Wang, J., Bina, R. W., Terwilliger, E. F., Hammer, R. P., & Nikulina, E. M. (2011, Spring). Knockdown of TrkB receptor expression in the nucleus accumbens prevents social defeat stress-induced cross-sensitization to psychostimulant. 2011 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience.
• Lacagnina, M. J., Terwilliger, E. F., Ren, X., Hammer, R. P., & Nikulina, E. M. (2010, Spring). Viral-mediated knockdown of BDNF in the medial prefrontal cortex prevents social defeat stress-induced amphetamine cross-sensitization in rats. 2010 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience.
• Maple, A. M., Britton, M., Nikulina, E. M., & Hammer, R. P. (2010, Spring). Repeated quinpirole treatment induces recovery of prepulse inhibition and delta FosB labeling in rat nucleus accumbens. 2010 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience.
• Nikulina, E. M., Lacagnina, M., Wang, J., Fanous, S., & Hammer, R. P. (2010, Spring). BDNF in the prefrontal cortex: involvement in psychostimulant- and social defeat stress-induced behavioral sensitization. CPDD Abstracts 72nd Annual Meeting.
• Wang, J., Nikulina, E. M., Ren, X., Terwilliger, E. F., & Hammer, R. P. (2010, Spring). BDNF over-expression in ventral tegmental area: essential role in social stress sensitization and elevated deltaFosB expression in rat nucleus accumbens. 2010 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience.
• Barnes, D. A., Nikulina, E. M., Miczek, K. A., & Hammer, R. P. (2008, Spring). Social stress exposure induces striatal adenosine A2A receptor expression. 2008 Society for Neuroscience Abstract Viewer Online.
• Fanous, S., Terwilliger, E., Hammer, R. P., & Nikulina, E. M. (2009, Spring). Depletion of brain-derived neurotrophic factor in the ventral tegmental area attenuates maintenance of cross-sensitization to amphetamine and modulates social behavior.. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience.
• Lacagnina, M., Fanous, S., Nikulina, E. M., & Hammer, R. P. (2009, Spring). Long-term amphetamine sensitization is associated with increased Fos activation and BDNF expression in cortical neurons innervating the VTA. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience.
• Nikulina, E. M., Lacagnina, M., Wang, J., & Hammer, R. P. (2009, Spring). Co-localization of BDNF and FosB/ΔFosB expression induced by social defeat stress in mesocorticolimbic brain regions. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience.
• Dickey, E. D., Shepherd, A., Barnes, D. A., & Hammer, R. P. (2008, Spring). Arc mRNA exhibits region-specific regulatory responses to cocaine self-administration, abstinence and extinction learning. 2008 Society for Neuroscience Abstract Viewer Online.
• Fanous, S., Terwilliger, E., Hammer, R. P., & Nikulina, E. M. (2008, Spring). BDNF knockdown in VTA prevents social stress-induced attenuation of weight gain in rats. 2008 Society for Neuroscience Abstract Viewer Online.
• Nikulina, E. M., Fanous, S., & Hammer, R. P. (2008, Spring). Naltrexone pretreatment prevents social stress-induced cross-sensitization and alters BDNF level in the VTA. 2008 Society for Neuroscience Abstract Viewer Online.
• Krupin, A. S., Green, T., Seigel, S. J., Nestler, E. J., & Hammer, R. P. (2007, Spring). : CREB phosphorylation in nucleus accumbens induced by chronic quinpirole treatment underlies recovery of sensorimotor gating in a rodent model of schizophrenia. TGen Scientific Retreat.
• Krupin, A. S., Green, T., Seigel, S. J., Nestler, E. J., & Hammer, R. P. (2007, Spring). Chronic quinpirole-induced CREB phosphorylation in NAc underlies recovery of sensorimotor gating in a rodent model of schizophrenia. 2007 Society for Neuroscience Abstract Viewer Online.
• Nikulina, E. M., Covington, H., Hammer, R. P., & Miczek, K. A. (2007, January). Brief episodes of social defeat stress: enduring sensitized cocaine intake and increased BDNF in ventral tegmental area and amygdala..
• Nikulina, E. M., Fanous, S., Terwilliger, E., Miczek, K. A., & Hammer, R. P. (2007, Spring). BDNF in dopaminergic areas as a substrate for long-term psychostimulant cross-sensitization after social defeat stress. European Behavioral Pharmacology Society.
• Arrillaga-Romany, I. C., & Hammer, R. P. (2006, Spring). Stress and strain and sensorimotor gating. Experimental Biology Abstract (ASPET).
• Fanous, S., Nikulina, E. M., & Hammer, R. P. (2006, Spring). Repeated social defeat stress induces activation of BDNF-containing neurons in rat medial prefrontal cortex. 2006 Society for Neuroscience Abstract Viewer Online.
• Hammer, R. P. (2006, Spring). Persistent neuroplasticity resulting from chronic D2-like receptor stimulation in rats. 2006 Spring Brain Conference Symposium.
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  Organizer
• Nikulina, E. M., Fanous, S., Miczek, K. A., & Hammer, R. P. (2006, Spring). Effect of intra-VTA BDNF on social defeat stress-induced sensitization in rats. 2006 Society for Neuroscience Abstract Viewer Online.
• Arrillaga-Romany, I. C., & Hammer, R. P. (2005, Spring). Corticotropin-releasing factor (CRF) impairs sensorimotor gating in the Sprague-Dawley rat: reversal by clozapine and raclopride,. 2005 Society for Neuroscience Abstract Viewer Online.
• Fanous, S., Hammer, R. P., & Nikulina, E. M. (2005, Spring). Timecourse of BDNF expression in the rat brain after repeated social defeat stress. 2005 Society for Neuroscience Abstract Viewer Online.
• Hammer, R. P., & Krupin, A. S. (2005, Spring). Repeated D2-like receptor agonist treatment prevents non-competitive NMDA antagonist-induced sensorimotor gating deficits in rats. 2005 Society for Neuroscience Abstract Viewer Online.
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  No. 913.9
• Hammer, R. P., & Krupin, A. S. (2005, Spring). Repeated ropinirole treatment produces sustained recovery from sensorimotor gating deficits in rats. 2005 Society for Neuroscience Abstract Viewer Online.
• Windsor, A. M., Arrillaga-Romany, I. C., & Hammer, R. P. (2005, Spring). Corticotropin-releasing factor-induced Fos expression is altered by raclopride pretreatment. 2005 Tufts University Summer Minority Scholars Symposium.
• Arrillaga-Romany, I., & Hammer, R. P. (2004, Spring). Long term exposure to stress levels of corticosterone does not produce sensorimotor gating deficits in rats. New England Pharmacologists Abstracts.
• Krupin, A. S., Hammer, R. P., Shoemaker, J. M., Goins, J. C., Bongiovanni, M. J., & Swerdlow, N. R. (2004, Spring). Heritable differences in the dopaminergic regulation of sensorimotor gating are not due to differences in D2-like receptor G protein function. 2004 Society for Neuroscience Abstract Viewer Online.
• Nikulina, E. M., Arrillaga-Romany, I., Fanous, S., Miczek, K. A., & Hammer, R. P. (2004, Spring). Sensitivity of mesocorticolimbic areas to µ-opioid receptor stimulation after repeated social defeat stress: Fos immunoreactivity in nucleus accumbens. 2004 Society for Neuroscience Abstract Viewer Online.
• Culm, K. E., & Hammer, R. P. (2003, Spring). Recovery of sensorimotor gating upon repeated quinpirole treatment is associated with increased PKA activity and phosphoCREB induction in the rat nucleus accumbens. 2003 Society for Neuroscience Abstract Viewer Online.
• Miczek, K. A., Nikulina, E. M., & Hammer, R. P. (2003, Spring). Brief episodes of social defeat stress, enduring neural and behavioral sensitization, and cocaine binges. Behavioral Psychology Society Abstracts.
• Nikulina, E. M., Covington, H. E., Arrillaga-Romany, I., Miczek, K. A., & Hammer, R. P. (2003, Spring). Long-term functional activation in amygdala induced by repeated social defeat stress. 2003 Society for Neuroscience Abstract Viewer Online.
• Zimmerman, E. I., & Hammer, R. P. (2003, Spring). Characterization of nucleus accumbens neurons involved in schizophrenia. Tufts University Summer Scholars Symposium.
• Culm, K. E., & Hammer, R. P. (2002, Spring). Involvement of cAMP-dependent protein kinase in the nucleus accumbens in sensorimotor gating deficits in rats. 2002 Society for Neuroscience Abstract Viewer Online.
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  Program No. 495.3
• Hammer, R. P., & Nikulina, E. M. (2002, Spring). Delayed and prolonged induction of FosB in limbic cortex following repeated social stress. 2002 Society for Neuroscience Abstract Viewer Online.
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  Program No. 669.10
• Nikulina, E. M., Goodhue, J. W., Covington, H. E., Miczek, K. A., & Hammer, R. P. (2002, Spring). Repeated social defeat stress induces prolonged behavioral sensitization and persistent Fos expression in mesolimbic regions of rats. 2002 Society for Neuroscience Abstract Viewer Online.
• Robinson, D. A., O'Brien, P. H., Greewala, R. G., Nikulina, E. M., Payne, D. D., Hammer, R. P., & Warner, K. G. (2002, Spring). . Warner: Differential expression of neuronal Fos protein following cold water drowning and controlled rewarming. American College of Surgery.
• Culm, K. E., & Hammer, R. P. (2001, Spring). Repeated quinpirole treatment attenuates sensorimotor gating deficits by decreasing G protein function. FASEB Abstracts.
• Onton, J. A., & Hammer, R. P. (2001, Spring). Chronic cocaine self-administration produces functional activation in neurons innervating the nucleus accumbens upon challenge after 21 days of withdrawal. Society for Neuroscience Abstracts.
• Nikulina, E. M., Miczek, K. A., & Hammer, R. P. (2000, Spring). Long-term consequences of repeated social stress on opioid modulation of mesocorticolimbic dopamine projections. Social Stress Meeting Abstracts.