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Social defeat disrupts reward learning and potentiates striatal nociceptin/orphanin FQ mRNA in rats

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Abstract

Rationale

Mood disorders can be triggered by stress and are characterized by deficits in reward processing, including disrupted reward learning (the ability to modulate behavior according to past rewards). Reward learning is regulated by the anterior cingulate cortex (ACC) and striatal circuits, both of which are implicated in the pathophysiology of mood disorders.

Objectives

Here, we assessed in rats the effects of a potent stressor (social defeat) on reward learning and gene expression in the ACC, ventral tegmental area (VTA), and striatum.

Methods

Adult male Wistar rats were trained on an operant probabilistic reward task (PRT) and then exposed to 3 days of social defeat before assessment of reward learning. After testing, the ACC, VTA, and striatum were dissected, and expression of genes previously implicated in stress was assessed.

Result

Social defeat blunted reward learning (manifested as reduced response bias toward a more frequently rewarded stimulus) and was associated with increased nociceptin/orphanin FQ (N/OFQ) peptide mRNA levels in the striatum and decreased Fos mRNA levels in the VTA. Moreover, N/OFQ peptide and nociceptin receptor mRNA levels in the ACC, VTA and striatum were inversely related to reward learning.

Conclusions

The behavioral findings parallel previous data in humans, suggesting that stress similarly disrupts reward learning in both species. Increased striatal N/OFQ mRNA in stressed rats characterized by impaired reward learning is consistent with accumulating evidence that antagonism of nociceptin receptors, which bind N/OFQ, has antidepressant-like effects. These results raise the possibility that nociceptin systems represent a molecular substrate through which stress produces reward learning deficits in mood disorders.

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References

  • American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders: DSM-5, 5th edn. American Psychiatric Association, American Psychiatric Association

  • Amiez C, Joseph JP, Procyk E (2006) Reward encoding in the monkey anterior cingulate cortex. Cereb Cortex 16:1040–1055

    Article  CAS  PubMed  Google Scholar 

  • Barch DM, Pagliaccio D, Luking K (2016) Mechanisms underlying motivational deficits in psychopathology: similarities and differences in depression and schizophrenia. Curr Top Behav Neurosci 27:411–449

    Article  PubMed  Google Scholar 

  • Berenbaum H, Connelly J (1993) The effect of stress on hedonic capacity. J Abnorm Psychol 102:474–481

    Article  CAS  PubMed  Google Scholar 

  • Berthele A, Platzer S, Dworzak D, Schadrack J, Mahal B, Buttner A, Assmus HP, Wurster K, Zieglgansberger W, Conrad B, Tolle TR (2003) [3H]-nociceptin ligand-binding and nociceptin opioid receptor mrna expression in the human brain. Neuroscience 121:629–640

    Article  CAS  PubMed  Google Scholar 

  • Bogdan R, Pizzagalli DA (2006) Acute stress reduces reward responsiveness: implications for depression. Biol Psychiatry 60:1147–1154

    Article  PubMed  PubMed Central  Google Scholar 

  • Bogdan R, Perlis RH, Fagerness J, Pizzagalli DA (2010) The impact of mineralocorticoid receptor ISO/VAL genotype (rs5522) and stress on reward learning. Genes Brain Behav 9:658–667

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bogdan R, Santesso DL, Fagerness J, Perlis RH, Pizzagalli DA (2011) Corticotropin-releasing hormone receptor type 1 (CRHR1) genetic variation and stress interact to influence reward learning. J Neurosci 31:13246–13254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bush G, Vogt BA, Holmes J, Dale AM, Greve D, Jenike MA, Rosen BR (2002) Dorsal anterior cingulate cortex: a role in reward-based decision making. Proc Natl Acad Sci U S A 99:523–528

    Article  CAS  PubMed  Google Scholar 

  • Carlezon WA Jr, Krystal AD (2016) Kappa-opioid antagonists for psychiatric disorders: from bench to clinical trials. Depress Anxiety 33:895–906

    Article  CAS  PubMed  Google Scholar 

  • Charney DS, Manji HK (2004) Life stress, genes, and depression: multiple pathways lead to increased risk and new opportunities for intervention. Sci STKE 2004: re5

  • Chartoff EH, Ebner SR, Sparrow A, Potter D, Baker PM, Ragozzino ME, Roitman MF (2016) Relative timing between kappa opioid receptor activation and cocaine determines the impact on reward and dopamine release. Neuropsychopharmacology 41:989–1002

    Article  CAS  PubMed  Google Scholar 

  • Der-Avakian A, Markou A (2012) The neurobiology of anhedonia and other reward-related deficits. Trends Neurosci 35:68–77

    Article  CAS  PubMed  Google Scholar 

  • Der-Avakian A, D'Souza MS, Pizzagalli DA, Markou A (2013) Assessment of reward responsiveness in the response bias probabilistic reward task in rats: implications for cross-species translational research. Transl Psychiatry 3:e297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Der-Avakian A, Mazei-Robison MS, Kesby JP, Nestler EJ, Markou A (2014) Enduring deficits in brain reward function after chronic social defeat in rats: susceptibility, resilience, and antidepressant response. Biol Psychiatry 76:542–549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Devine DP, Watson SJ, Akil H (2001) Nociceptin/orphanin FQ regulates neuroendocrine function of the limbic-hypothalamic-pituitary-adrenal axis. Neuroscience 102:541–553

    Article  CAS  PubMed  Google Scholar 

  • Donahue RJ, Muschamp JW, Russo SJ, Nestler EJ, Carlezon WA Jr (2014) Effects of striatal DeltaFosB overexpression and ketamine on social defeat stress-induced anhedonia in mice. Biol Psychiatry 76:550–558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dunlop BW, Nemeroff CB (2007) The role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry 64:327–337

    Article  CAS  PubMed  Google Scholar 

  • Ernst M, Nelson EE, McClure EB, Monk CS, Munson S, Eshel N, Zarahn E, Leibenluft E, Zametkin A, Towbin K, Blair J, Charney D, Pine DS (2004) Choice selection and reward anticipation: an fMRI study. Neuropsychologia 42:1585–1597

    Article  PubMed  Google Scholar 

  • Gavioli EC, Marzola G, Guerrini R, Bertorelli R, Zucchini S, De Lima TC, Rae GA, Salvadori S, Regoli D, Calo G (2003) Blockade of nociceptin/orphanin FQ-NOP receptor signalling produces antidepressant-like effects: pharmacological and genetic evidences from the mouse forced swimming test. Eur J Neurosci 17:1987–1990

    Article  CAS  PubMed  Google Scholar 

  • Gavioli EC, Vaughan CW, Marzola G, Guerrini R, Mitchell VA, Zucchini S, De Lima TC, Rae GA, Salvadori S, Regoli D, Calo G (2004) Antidepressant-like effects of the nociceptin/orphanin FQ receptor antagonist UFP-101: new evidence from rats and mice. Naunyn Schmiedeberg's Arch Pharmacol 369:547–553

    Article  CAS  Google Scholar 

  • Glimcher PW (2011) Understanding dopamine and reinforcement learning: the dopamine reward prediction error hypothesis. Proc Natl Acad Sci U S A 108(Suppl 3):15647–15654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gold JM, Waltz JA, Prentice KJ, Morris SE, Heerey EA (2008) Reward processing in schizophrenia: a deficit in the representation of value. Schizophr Bull 34:835–847

    Article  PubMed  PubMed Central  Google Scholar 

  • Green TA, Alibhai IN, Roybal CN, Winstanley CA, Theobald DE, Birnbaum SG, Graham AR, Unterberg S, Graham DL, Vialou V, Bass CE, Terwilliger EF, Bardo MT, Nestler EJ (2010) Environmental enrichment produces a behavioral phenotype mediated by low cyclic adenosine monophosphate response element binding (CREB) activity in the nucleus accumbens. Biol Psychiatry 67:28–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu H, Hu D, Hong XR, Mao J, Cui Y, Hui N, Sha JY (2003) Changes and significance of orphanin and serotonin in patients with postpartum depression. Zhonghua Fu Chan Ke Za Zhi 38:727–728

    PubMed  Google Scholar 

  • Hollis F, Kabbaj M (2014) Social defeat as an animal model for depression. ILAR J 55:221–232

    Article  CAS  PubMed  Google Scholar 

  • Kendler KS, Karkowski LM, Prescott CA (1999) Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 156:837–841

    Article  CAS  PubMed  Google Scholar 

  • Kennerley SW, Walton ME, Behrens TE, Buckley MJ, Rushworth MF (2006) Optimal decision making and the anterior cingulate cortex. Nat Neurosci 9:940–947

    Article  CAS  PubMed  Google Scholar 

  • Koizumi M, Midorikawa N, Takeshima H, Murphy NP (2004a) Exogenous, but not endogenous nociceptin modulates mesolimbic dopamine release in mice. J Neurochem 89:257–263

    Article  CAS  PubMed  Google Scholar 

  • Koizumi M, Sakoori K, Midorikawa N, Murphy NP (2004b) The NOP (ORL1) receptor antagonist Compound B stimulates mesolimbic dopamine release and is rewarding in mice by a non-NOP-receptor-mediated mechanism. Br J Pharmacol 143:53–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lambert G, Johansson M, Agren H, Friberg P (2000) Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: evidence in support of the catecholamine hypothesis of mood disorders. Arch Gen Psychiatry 57:787–793

    Article  CAS  PubMed  Google Scholar 

  • Lezak KR, Roman CW, Braas KM, Schutz KC, Falls WA, Schulkin J, May V, Hammack SE (2014) Regulation of bed nucleus of the stria terminalis PACAP expression by stress and corticosterone. J Mol Neurosci 54:477–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu WH, Chan RC, Wang LZ, Huang J, Cheung EF, Gong QY, Gollan JK (2011) Deficits in sustaining reward responses in subsyndromal and syndromal major depression. Prog Neuro-Psychopharmacol Biol Psychiatry 35:1045–1052

    Article  Google Scholar 

  • Lohith TG, Zoghbi SS, Morse CL, Araneta MF, Barth VN, Goebl NA, Tauscher JT, Pike VW, Innis RB, Fujita M (2012) Brain and whole-body imaging of nociceptin/orphanin FQ peptide receptor in humans using the PET ligand 11C-NOP-1A. J Nucl Med 53:385–392

    Article  CAS  PubMed  Google Scholar 

  • Lohith TG, Zoghbi SS, Morse CL, Araneta MD, Barth VN, Goebl NA, Tauscher JT, Pike VW, Innis RB, Fujita M (2014) Retest imaging of [11C]NOP-1A binding to nociceptin/orphanin FQ peptide (NOP) receptors in the brain of healthy humans. NeuroImage 87:89–95

    Article  CAS  PubMed  Google Scholar 

  • Maia TV, Frank MJ (2011) From reinforcement learning models to psychiatric and neurological disorders. Nat Neurosci 14:154–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murphy NP, Maidment NT (1999) Orphanin FQ/nociceptin modulation of mesolimbic dopamine transmission determined by microdialysis. J Neurochem 73:179–186

    Article  CAS  PubMed  Google Scholar 

  • Murphy NP, Ly HT, Maidment NT (1996) Intracerebroventricular orphanin FQ/nociceptin suppresses dopamine release in the nucleus accumbens of anaesthetized rats. Neuroscience 75:1–4

    Article  CAS  PubMed  Google Scholar 

  • Murphy NP, Tan AM, Lam HA, Maidment NT (2004) Nociceptin/orphanin FQ modulation of rat midbrain dopamine neurons in primary culture. Neuroscience 127:929–940

    Article  CAS  PubMed  Google Scholar 

  • Muschamp JW, Van't Veer A, Parsegian A, Gallo MS, Chen M, Neve RL, Meloni EG, Carlezon WA Jr (2011) Activation of CREB in the nucleus accumbens shell produces anhedonia and resistance to extinction of fear in rats. J Neurosci 31:3095–3103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nativio P, Pascale E, Maffei A, Scaccianoce S, Passarelli F (2012) Effect of stress on hippocampal nociceptin expression in the rat. Stress 15:378–384

    Article  CAS  PubMed  Google Scholar 

  • Neal CR Jr, Mansour A, Reinscheid R, Nothacker HP, Civelli O, Akil H, Watson SJ Jr (1999) Opioid receptor-like (ORL1) receptor distribution in the rat central nervous system: comparison of ORL1 receptor mRNA expression with (125)I-[(14)Tyr]-orphanin FQ binding. J Comp Neurol 412:563–605

    Article  CAS  PubMed  Google Scholar 

  • Nestler EJ, Carlezon WA Jr (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59:1151–1159

    Article  CAS  PubMed  Google Scholar 

  • Nikolova Y, Bogdan R, Pizzagalli DA (2012) Perception of a naturalistic stressor interacts with 5-HTTLPR/rs25531 genotype and gender to impact reward responsiveness. Neuropsychobiology 65:45–54

    Article  PubMed  Google Scholar 

  • Nutt DJ (2006) The role of dopamine and norepinephrine in depression and antidepressant treatment. J Clin Psychiatry 67(Suppl 6):3–8

    CAS  PubMed  Google Scholar 

  • Onn SP, Wang XB (2005) Differential modulation of anterior cingulate cortical activity by afferents from ventral tegmental area and mediodorsal thalamus. Eur J Neurosci 21:2975–2992

    Article  PubMed  Google Scholar 

  • Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press/Elsevier, Academic Press/Elsevier

  • Pechtel P, Dutra SJ, Goetz EL, Pizzagalli DA (2013) Blunted reward responsiveness in remitted depression. J Psychiatr Res 47:1864–1869

    Article  PubMed  PubMed Central  Google Scholar 

  • Pergadia ML, Der-Avakian A, D'Souza MS, Madden PA, Heath AC, Shiffman S, Markou A, Pizzagalli DA (2014) Association between nicotine withdrawal and reward responsiveness in humans and rats. JAMA Psychiatry 71:1238–1245

    Article  PubMed  PubMed Central  Google Scholar 

  • Pizzagalli DA, Jahn AL, O'Shea JP (2005) Toward an objective characterization of an anhedonic phenotype: a signal-detection approach. Biol Psychiatry 57:319–327

    Article  PubMed  PubMed Central  Google Scholar 

  • Pizzagalli DA, Bogdan R, Ratner KG, Jahn AL (2007) Increased perceived stress is associated with blunted hedonic capacity: potential implications for depression research. Behav Res Ther 45:2742–2753

    Article  PubMed  PubMed Central  Google Scholar 

  • Pizzagalli DA, Goetz E, Ostacher M, Iosifescu DV, Perlis RH (2008a) Euthymic patients with bipolar disorder show decreased reward learning in a probabilistic reward task. Biol Psychiatry 64:162–168

    Article  PubMed  PubMed Central  Google Scholar 

  • Pizzagalli DA, Iosifescu D, Hallett LA, Ratner KG, Fava M (2008b) Reduced hedonic capacity in major depressive disorder: evidence from a probabilistic reward task. J Psychiatr Res 43:76–87

    Article  PubMed  PubMed Central  Google Scholar 

  • Pliakas AM, Carlson RR, Neve RL, Konradi C, Nestler EJ, Carlezon WA Jr (2001) Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element-binding protein expression in nucleus accumbens. J Neurosci 21:7397–7403

    CAS  PubMed  PubMed Central  Google Scholar 

  • Post A, Smart TS, Krikke-Workel J, Dawson GR, Harmer CJ, Browning M, Jackson K, Kakar R, Mohs R, Statnick M, Wafford K, McCarthy A, Barth V, Witkin JM (2016) A selective nociceptin receptor antagonist to treat depression: evidence from preclinical and clinical studies. Neuropsychopharmacology 41:2624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Redrobe JP, Calo G, Regoli D, Quirion R (2002) Nociceptin receptor antagonists display antidepressant-like properties in the mouse forced swimming test. Naunyn Schmiedeberg's Arch Pharmacol 365:164–167

    Article  CAS  Google Scholar 

  • Rizzi A, Gavioli EC, Marzola G, Spagnolo B, Zucchini S, Ciccocioppo R, Trapella C, Regoli D, Calo G (2007) Pharmacological characterization of the nociceptin/orphanin FQ receptor antagonist SB-612111 [(−)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrah ydro-5H-benzocyclohepten-5-ol]: in vivo studies. J Pharmacol Exp Ther 321:968–974

    Article  CAS  PubMed  Google Scholar 

  • Roman CW, Lezak KR, Hartsock MJ, Falls WA, Braas KM, Howard AB, Hammack SE, May V (2014) PAC1 receptor antagonism in the bed nucleus of the stria terminalis (BNST) attenuates the endocrine and behavioral consequences of chronic stress. Psychoneuroendocrinology 47:151–165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rushworth MF, Behrens TE, Rudebeck PH, Walton ME (2007) Contrasting roles for cingulate and orbitofrontal cortex in decisions and social behaviour. Trends Cogn Sci 11:168–176

    Article  CAS  PubMed  Google Scholar 

  • Rygula R, Abumaria N, Havemann-Reinecke U, Ruther E, Hiemke C, Zernig G, Fuchs E, Flugge G (2008) Pharmacological validation of a chronic social stress model of depression in rats: effects of reboxetine, haloperidol and diazepam. Behav Pharmacol 19:183–196

    Article  CAS  PubMed  Google Scholar 

  • Santesso DL, Dillon DG, Birk JL, Holmes AJ, Goetz E, Bogdan R, Pizzagalli DA (2008) Individual differences in reinforcement learning: behavioral, electrophysiological, and neuroimaging correlates. NeuroImage 42:807–816

    Article  PubMed  PubMed Central  Google Scholar 

  • Santesso DL, Evins AE, Frank MJ, Schetter EC, Bogdan R, Pizzagalli DA (2009) Single dose of a dopamine agonist impairs reinforcement learning in humans: evidence from event-related potentials and computational modeling of striatal-cortical function. Hum Brain Mapp 30:1963–1976

    Article  PubMed  PubMed Central  Google Scholar 

  • Seo H, Lee D (2007) Temporal filtering of reward signals in the dorsal anterior cingulate cortex during a mixed-strategy game. J Neurosci 27:8366–8377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sim LJ, Childers SR (1997) Anatomical distribution of mu, delta, and kappa opioid- and nociceptin/orphanin FQ-stimulated [35S]guanylyl-5'-O-(gamma-thio)-triphosphate binding in guinea pig brain. J Comp Neurol 386:562–572

    Article  CAS  PubMed  Google Scholar 

  • Sim LJ, Xiao R, Childers SR (1996) Identification of opioid receptor-like (ORL1) peptide-stimulated [35S]GTP gamma S binding in rat brain. Neuroreport 7:729–733

    Article  CAS  PubMed  Google Scholar 

  • Swanson LW (1982) The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res Bull 9:321–353

    Article  CAS  PubMed  Google Scholar 

  • Treadway MT, Zald DH (2011) Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev 35:537–555

    Article  PubMed  Google Scholar 

  • Tripp G, Alsop B (1999) Sensitivity to reward frequency in boys with attention deficit hyperactivity disorder. J Clin Child Psychol 28:366–375

    Article  CAS  PubMed  Google Scholar 

  • Venzala E, Garcia-Garcia AL, Elizalde N, Delagrange P, Tordera RM (2012) Chronic social defeat stress model: behavioral features, antidepressant action, and interaction with biological risk factors. Psychopharmacology 224:313–325

    Article  CAS  PubMed  Google Scholar 

  • Vitale G, Ruggieri V, Filaferro M, Frigeri C, Alboni S, Tascedda F, Brunello N, Guerrini R, Cifani C, Massi M (2009) Chronic treatment with the selective NOP receptor antagonist [Nphe 1, Arg 14, Lys 15]N/OFQ-NH 2 (UFP-101) reverses the behavioural and biochemical effects of unpredictable chronic mild stress in rats. Psychopharmacology 207:173–189

    Article  CAS  PubMed  Google Scholar 

  • Vrieze E, Pizzagalli DA, Demyttenaere K, Hompes T, Sienaert P, de Boer P, Schmidt M, Claes S (2013) Reduced reward learning predicts outcome in major depressive disorder. Biol Psychiatry 73:639–645

    Article  PubMed  Google Scholar 

  • Wang LN, Liu LF, Zhang JX, Zhao GF (2009) Plasma levels of nociceptin/orphanin FQ in patients with bipolar disorders and health adults. Zhonghua Yi Xue Za Zhi 89:916–918

    CAS  PubMed  Google Scholar 

  • Whitton AE, Treadway MT, Pizzagalli DA (2015) Reward processing dysfunction in major depression, bipolar disorder and schizophrenia. Curr Opin Psychiatry 28:7–12

    Article  PubMed  PubMed Central  Google Scholar 

  • Whitton AE, Kakani P, Foti D, Veer AV, Haile A, Crowley DJ, Pizzagalli DA (2016) Blunted neural responses to reward in remitted major depression: a high-density event-related potential study. Biol Psychiatry Cogn Neurosci Neuroimaging 1:87–95

    Article  PubMed  PubMed Central  Google Scholar 

  • Witkin JM, Statnick MA, Rorick-Kehn LM, Pintar JE, Ansonoff M, Chen Y, Tucker RC, Ciccocioppo R (2014) The biology of nociceptin/orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence. Pharmacol Ther 141:283–299

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Ms. Jessica Benedict for technical assistance.

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Authors and Affiliations

  1. Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA

    Andre Der-Avakian & Athina Markou

  2. Department of Pharmaceutical and Biomedical Sciences, Ohio Northern University, Ada, OH, USA

    Manoranjan S. D’Souza

  3. McLean Hospital, Belmont, MA, USA

    David N. Potter, Elena H. Chartoff, William A. Carlezon Jr & Diego A. Pizzagalli

  4. Department of Psychiatry, Harvard Medical School, Belmont, MA, USA

    David N. Potter, Elena H. Chartoff, William A. Carlezon Jr & Diego A. Pizzagalli

Authors
  1. Andre Der-Avakian
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  2. Manoranjan S. D’Souza
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  3. David N. Potter
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  4. Elena H. Chartoff
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  5. William A. Carlezon Jr
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  6. Diego A. Pizzagalli
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  7. Athina Markou
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Correspondence to Andre Der-Avakian or Diego A. Pizzagalli.

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Conflict of interest

Over the past 3 years, Dr. Pizzagalli received consulting fees from Akili Interactive Labs, BlackThorn Therapeutics, Pfizer, and Posit Science, for activities unrelated to the current research. Dr. Markou received contract research support from Bristol-Myers Squibb Co., and honoraria/consulting fees from Abbott GmbH and Company, AstraZeneca, and Pfizer during the past 2 years for projects unrelated to the present research. Dr. Markou also had a patent on the use of metabotropic glutamate compounds for the treatment of nicotine dependence that is unrelated to the present research. Dr. Carlezon discloses that he is an inventor on several patents that claim the use of selective kappa opioid ligands to treat psychiatric illness (Assignee: McLean Hospital) and during the past 2 years, has received compensation as a consultant for Cerecor. No other authors report any conflicts of interest.

Support

This work was supported by National Institutes of Health grants R21MH078979 (DAP) and R01MH063266 (WAC). Dr. Pizzagalli was further supported by R01MH0958092 and R37MH068376. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Diego A. Pizzagalli and Athina Markou contributed equally as senior authors

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Der-Avakian, A., D’Souza, M.S., Potter, D.N. et al. Social defeat disrupts reward learning and potentiates striatal nociceptin/orphanin FQ mRNA in rats. Psychopharmacology 234, 1603–1614 (2017). https://doi.org/10.1007/s00213-017-4584-y

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