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Social defeat stress in rats: escalation of cocaine and “speedball” binge self-administration, but not heroin

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Abstract

Rationale

Exposure to intermittent episodes of social defeat stress can increase drug seeking and leads to intense drug taking in rats.

Objectives

This study investigated the consequences of repeated, intermittent social defeat stress on patterns of drug self-administration in rats with access to heroin, cocaine, or a heroin–cocaine combination (“speedball”).

Methods

Male Long-Evans rats were either handled (controls) or subjected to 25-min social defeat stress episodes on days 1, 4, 7, and 10 during confrontations with an aggressive resident. Ten days following the last defeat, rats were assessed for locomotor cross-sensitization in response to heroin or cocaine. Animals were then prepared with intrajugular catheters for drug self-administration. Separate groups of controls and defeated rats were examined for self-administration of heroin (experiment 1), a heroin–cocaine combination (experiment 2), or cocaine (experiment 3). Drug self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement during limited access sessions or a 24-h unlimited access binge.

Results

Rats with a history of intermittent social defeat stress showed sensitized locomotor behavior when challenged with heroin or cocaine relative to controls. During the 24-h binge session, defeated rats escalated cocaine-taking behavior (ca. 110 mg/kg vs. 66 mg/kg in controls), persisted in self-administering cocaine or the heroin–cocaine mixture for more hours, and showed a tendency for increased heroin–cocaine intake, but no effects on heroin taking.

Conclusions

A history of social defeat stress seems to preferentially promote escalated intake of cocaine but not heroin, unless a heroin–cocaine combination is available.

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References

  • Anstrom KK, Miczek KA, Budygin EA (2009) Increased phasic dopamine signaling in the mesolimbic pathway during social defeat in rats. Neuroscience 161:3–12

    Article  PubMed  CAS  Google Scholar 

  • Arnold JM, Roberts DCS (1997) A critique of fixed and progressive ratio schedules used to examine the neural subsrtrates of drug reinforcement. Pharmacol Biochem Behav 57:441–447

    Article  PubMed  CAS  Google Scholar 

  • Brown SA, Vik PW, Patterson TL, Grant I, Schuckit MA (1995) Stress, vulnerability and adult alcohol relapse. J Stud Alcohol 56:538–545

    PubMed  CAS  Google Scholar 

  • Caprioli D, Celentano M, Paolone G, Badiani A (2007) Modeling the role of environment in addiction. Prog Neuropsychopharmacol Biol Psychiatry 31:1639–1653

    Article  PubMed  Google Scholar 

  • Caprioli D, Celentano M, Paolone G, Lucantonio F, Bari A, Nencini P, Badiani A (2008) Opposite environmental regulation of heroin and amphetamine self-administration in the rat. Psychopharmacology 198:395–404

    Article  PubMed  CAS  Google Scholar 

  • Celentano M, Caprioli D, Dipasquale P, Cardillo V, Nencini P, Gaetani S, Badiani A (2009) Drug context differently regulates cocaine versus heroin self-administration and cocaine- versus heroin-induced Fos mRNA expression in the rat. Psychopharmacology 204:349–360

    Article  PubMed  CAS  Google Scholar 

  • Covington HE III, Miczek KA (2001) Repeated social-defeat stress, cocaine or morphine. Effects on locomotor sensitization and intravenous cocaine self-administration “binges”. Psychopharmacology 158:388–398

    Article  PubMed  CAS  Google Scholar 

  • Covington HE III, Miczek KA (2005) Ïntense cocaine self-administration after episodic social defeat stress, but not after aggressive behavior: dissociation from corticosterone activation. Psychopharmacology 183:331–340

    Article  PubMed  CAS  Google Scholar 

  • Covington HE III, Kikusui T, Goodhue J, Nikulina EM, Hammer RP Jr, Miczek KA (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 30:310–321

    Article  PubMed  CAS  Google Scholar 

  • Covington HE III, Tropea TF, Rajadhyaksha AM, Kosofsky BE, Miczek KA (2008) NMDA receptors in the rat VTA: a critical site for social stress to intensify cocaine taking. Psychopharmacology 197:203–216

    Article  PubMed  CAS  Google Scholar 

  • Darke S, Hall W (1995) Levels and correlates of polydrug use among heroin users and regular amphetamine users. Drug Alcohol Depend 39:231–235

    Article  PubMed  CAS  Google Scholar 

  • del Rosario CN, Pacchioni AM, Cancela LM (2002) Influence of acute or repeated restraint stress on morphine-induced locomotion: involvement of dopamine, opioid and glutamate receptors. Behav Brain Res 134:229–238

    Article  PubMed  Google Scholar 

  • Dembo R, Williams L, Berry E, Getreu A, Washburn M, Wish ED, Schmeidler J (1988) The relationship between physical and sexual abuse and illicit drug use: a replication among a new sample of youths entering a juvenile detention center. Int J Addict 23:1101–1123

    PubMed  CAS  Google Scholar 

  • Deroche V, Piazza PV, Casolini P, Maccari S, Le Moal M, Simon H (1992) Stress-induced sensitization to amphetamine and morphine psychomotor effects depend on stress-induced corticosterone secretion. Brain Res 598:343–348

    Article  PubMed  CAS  Google Scholar 

  • Deroche V, Marinelli M, Maccari S, Lemoal M, Simon H, Piazza PV (1995) Stress-induced sensitization and glucocorticoids.1. Sensitization of dopamine-dependent locomotor effects of amphetamine and morphine depends on stress-induced corticosterone secretion. J Neurosci 15:7181–7188

    PubMed  CAS  Google Scholar 

  • Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85:5274–5278

    Article  PubMed  Google Scholar 

  • Duvauchelle CL, Sapoznik T, Kornetsky C (1998) The synergistic effects of combining cocaine and heroin (“speedball”) using a progressive-ratio schedule of drug reinforcement. Pharmacol Biochem Behav 61:297–302

    Article  PubMed  CAS  Google Scholar 

  • Foltin RW, Fischman MW (1992) The cardiovascular and subjective effects of intravenous cocaine and morphine combinations in humans. J Pharmacol Exp Ther 261:623–632

    PubMed  CAS  Google Scholar 

  • Goeders NE, Guerin GF (1994) Non-contingent electric footshock facilitates the acquisition of intravenous cocain self-administration in rats. Psychopharmacology 114:63–70

    Article  PubMed  CAS  Google Scholar 

  • Grimm JW, Lu L, Hayashi T, Hope BT, Su TP, Shaham Y (2003) Time-dependent increases in brain-derived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: implications for incubation of cocaine craving. J Neurosci 23:742–747

    PubMed  CAS  Google Scholar 

  • Haney M, Maccari S, Le Moal M, Simon H, Piazza PV (1995) Social stress increases the acquisition of cocaine self-administration in male and female rats. Brain Res 698:46–52

    Article  PubMed  CAS  Google Scholar 

  • Harrison PA, Fulkerson JA, Beebe TJ (1997) Multiple substance use among adolescent physical and sexual abuse victims. Child Abuse Negl 21:529–539

    Article  PubMed  CAS  Google Scholar 

  • Hartel DM, Schoenbaum EE, Selwyn PA, Kline J, Davenny K, Klein RS, Friedland GH (1995) Heroin use during methadone maintenance treatment: the importance of methadone dose and cocaine use. Am J Public Health 85:83–88

    Article  PubMed  CAS  Google Scholar 

  • Hasin DS, Grant BF, Endicott J, Harford TC (1988) Cocaine and heroin dependence compared in poly-drug abusers. Am J Public Health 78:567–569

    Article  PubMed  CAS  Google Scholar 

  • Hemby SE, Martin TJ, Co C, Dworkin SI, Smith JE (1995) The effects of intravenous heroin administration on extracellular nucleus accumbens dopamine concentrations as determined by in vivo microdialysis. J Pharmacol Exp Ther 273:591–598

    PubMed  CAS  Google Scholar 

  • Hemby SE, Co C, Dworkin SI, Smith JE (1999) Synergistic elevations in nucleus accumbens extracellular dopamine concentrations during self-administration of cocaine/heroin combinations (Speedball) in rats. J Pharmacol Exp Ther 288:274–280

    PubMed  CAS  Google Scholar 

  • Hubner CB, Koob GF (1990) Bromocriptine produces decreases in cocaine self-administration in the rat. Neuropsychopharmacology 3:101–108

    PubMed  CAS  Google Scholar 

  • Jacobsen LK, Southwick SM, Kosten TR (2001) Substance use disorders in patients with posttraumatic stress disorder: a review of the literature. Am J Psychiatry 158:1184–1190

    Article  PubMed  CAS  Google Scholar 

  • Kabbaj M, Norton CS, Kollack-Walker S, Watson SJ, Robinson TE, Akil H (2001) Social defeat alters the acquisition of cocaine self-administration in rats: role of individual differences in cocaine-taking behavior. Psychopharmacology 158:382–387

    Article  PubMed  CAS  Google Scholar 

  • Koob G, Kreek MJ (2007) Stress, dysregulation of drug reward pathways, and the transition to drug dependence. Am J Psychiatry 164:1149–1159

    Article  PubMed  Google Scholar 

  • Kosten TR, Gawin FH, Rounsaville BJ, Kleber HD (1986) Cocaine abuse among opioid addicts: demographic and diagnostic factors in treatment. Am J Drug Alcohol Abuse 12:1–16

    Article  PubMed  CAS  Google Scholar 

  • Kosten TA, Miserendino MJ, Kehoe P (2000) Enhanced acquisition of cocaine self-administration in adult rats with neonatal isolation stress experience. Brain Res 875:44–50

    Article  PubMed  CAS  Google Scholar 

  • Leri F, Stewart J, Tremblay A, Bruneau J (2004) Heroin and cocaine co-use in a group of injection drug users in Montreal. J Psychiatry Neurosci 29:40–47

    PubMed  Google Scholar 

  • Leyton M, Stewart J (1990) Preexposure to foot-shock sensitizes the locomotor response to subsequent systemic morphine and intra-nucleus accumbens amphetamine. Pharmacol Biochem Behav 37:303–310

    Article  PubMed  CAS  Google Scholar 

  • Mello NK, Lukas SE, Bree MP, Mendelson JH (1988) Progressive ratio performance maintained by buprenorphine, heroin and methadone in Macaque monkeys. Drug Alcohol Depend 21:81–97

    Article  PubMed  CAS  Google Scholar 

  • Mello NK, Negus SS, Lukas SE, Mendelson JH, Sholar JW, Drieze J (1995) A primate model of polydrug abuse: cocaine and heroin combinations. J Pharmacol Exp Ther 274:1325–1337

    PubMed  CAS  Google Scholar 

  • Miczek KA (1979) A new test for aggression in rats without aversive stimulation: differential effects of d-amphetamine and cocaine. Psychopharmacology 60:253–259

    Article  PubMed  CAS  Google Scholar 

  • Miczek KA, Mutschler NH (1996) Activational effects of social stress on IV cocaine self-administration in rats. Psychopharmacology 128:256–264

    Article  PubMed  CAS  Google Scholar 

  • Miczek KA, Mutschler NH, Van Erp AMM, Blank AD, McInerney SC (1999a) d-Amphetamine “cue” generalizes to social defeat stress: sensitization and role of accumbens dopamine. Psychopharmacology 147:190–199

    Article  PubMed  CAS  Google Scholar 

  • Miczek KA, Nikulina E, Kream RM, Carter G, Espejo EF (1999b) Behavioral sensitization to cocaine after a brief social defeat stress: c- fos expression in the PAG. Psychopharmacology 141:225–234

    Article  PubMed  CAS  Google Scholar 

  • Miczek KA, Yap JJ, Covington HE III (2008) Social stress, therapeutics and drug abuse: preclinical models of escalated and depressed intake. Pharmacol Ther 120:102–128

    Article  PubMed  CAS  Google Scholar 

  • National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington DC

    Google Scholar 

  • Nikulina EM, Marchand JE, Kream RM, Miczek KA (1998) Behavioral sensitization to cocaine after a brief social stress is accompanied by changes in fos expression in the murine brainstem. Brain Res 810:200–210

    Article  PubMed  CAS  Google Scholar 

  • Nikulina EM, Hammer RP Jr, Miczek KA, Kream RM (1999) Social defeat stress increases expression of mu-opioid receptor mRNA in rat ventral tegmental area. NeuroReport 10:3015–3019

    Article  PubMed  CAS  Google Scholar 

  • Nikulina EM, Covington HE III, Ganschow L, Hammer RP Jr, Miczek KA (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 123:857–865

    Article  PubMed  CAS  Google Scholar 

  • Nikulina EM, Miczek KA, Hammer RP Jr (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 30:1096–1103

    Article  PubMed  CAS  Google Scholar 

  • Piazza PV, Deminiere JM, Le Moal M, Simon H (1990) Stress- and pharmacologically- induced behavioral sensitization increases vulnerability to acquisition of amphetamine self-administration. Brain Res 514:22–26

    Article  PubMed  CAS  Google Scholar 

  • Quadros IM, Miczek KA (2009) Two modes of intense cocaine bingeing: increased persistence after social defeat stress and increased rate of intake due to extended access conditions in rats. Psychopharmacology 206:109–121

    Article  PubMed  CAS  Google Scholar 

  • Ramsey NF, van Ree JM (1993) Emotional but not physical stress enhances intravenous cocaine self- administration in drug-naive rats. Brain Res 608:216–222

    Article  PubMed  CAS  Google Scholar 

  • Ranaldi R, Munn E (1998) Polydrug self-administration in rats: cocaine-heroin is more rewarding than cocaine alone. NeuroReport 9:2463–2466

    Article  PubMed  CAS  Google Scholar 

  • Ranaldi R, Wise RA (2000) Intravenous self-administration of methamphetamine-heroin (speedball) combinations under a progressive-ratio schedule of reinforcement in rats. NeuroReport 11:2621–2623

    Article  PubMed  CAS  Google Scholar 

  • Richardson NR, Roberts DCS (1996) Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods 66:1–11

    Article  PubMed  CAS  Google Scholar 

  • Roberts DC, Bennett SA (1993) Heroin self-administration in rats under a progressive ratio schedule of reinforcement. Psychopharmacology 111:215–218

    Article  PubMed  CAS  Google Scholar 

  • Rouge-Pont F, Marinelli M, Le Moal M, Simon H, Piazza PV (1995) Stress-induced sensitization and glucocorticoids.2. Sensitization of the increase in extracellular dopamine induced by cocaine depends on stress-induced corticosterone secretion. J Neurosci 15:7189–7195

    PubMed  CAS  Google Scholar 

  • Rowlett JK, Woolverton WL (1997) Self-administration of cocaine and heroin combinations by rhesus monkeys responding under a progressive-ratio schedule. Psychopharmacology 133:363–371

    Article  PubMed  CAS  Google Scholar 

  • Rowlett JK, Wilcox KM, Woolverton WL (1998) Self-administration of cocaine-heroin combinations by rhesus monkeys: antagonism by naltrexone. J Pharmacol Exp Ther 286:61–69

    PubMed  CAS  Google Scholar 

  • Shaham Y, Stewart J (1994) Exposure to mild stress enhances the reinforcing efficacy of intravenous heroin self-administration in rats. Psychopharmacology 114:523–527

    Article  PubMed  CAS  Google Scholar 

  • Shalev U, Grimm JW, Shaham Y (2002) Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacol Rev 54:1–42

    Article  PubMed  CAS  Google Scholar 

  • Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology 158:343–359

    Article  PubMed  CAS  Google Scholar 

  • Smith JE, Co C, Coller MD, Hemby SE, Martin TJ (2006) Self-administered heroin and cocaine combinations in the rat: additive reinforcing effects-supra-additive effects on nucleus accumbens extracellular dopamine. Neuropsychopharmacology 31:139–150

    Article  PubMed  CAS  Google Scholar 

  • Stohr T, Almeida OFX, Landgraf R, Shippenberg TS, Holsboer F, Spanagel R (1999) Stress- and corticosteroid-induced modulation of the locomotor response to morphine in rats. Behav Brain Res 103:85–93

    Article  PubMed  CAS  Google Scholar 

  • Tidey JW, Miczek KA (1997) Acquisition of cocaine self-administration after social stress: role of accumbens dopamine. Psychopharmacology 130:203–212

    Article  PubMed  CAS  Google Scholar 

  • Tornatzky W, Miczek KA (1993) Long-term impairment of autonomic circadian rhythms after brief intermittent social stress. Physiol Behav 53:983–993

    Article  PubMed  CAS  Google Scholar 

  • Ward SJ, Morgan D, Roberts DC (2005) Comparison of the reinforcing effects of cocaine and cocaine/heroin combinations under progressive ratio and choice schedules in rats. Neuropsychopharmacology 30:286–295

    Article  PubMed  CAS  Google Scholar 

  • Wise RA, Newton P, Leeb K, Burnette B, Pocock D, Justice JB Jr (1995) Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats. Psychopharmacology 120:10–20

    Article  PubMed  CAS  Google Scholar 

  • Yap JJ, Miczek KA (2007) Social defeat stress, sensitization, and intravenous cocaine self-administration in mice. Psychopharmacology 192:261–273

    Article  PubMed  CAS  Google Scholar 

  • Yap JJ, Takase LF, Kochman LJ, Fornal CA, Miczek KA, Jacobs BL (2006) Repeated brief social defeat episodes in mice: effects on cell proliferation in the dentate gyrus. Behav Brain Res 172:344–350

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Psychology, Tufts University, Bacon Hall, 530 Boston Ave, Medford, MA, 02155, USA

    Fabio C. Cruz, Isabel M. Quadros, Koen Hogenelst & Klaus A. Miczek

  2. School of Pharmaceutical Sciences, UNESP – São Paulo State University, Araraquara, SP, Brazil

    Fabio C. Cruz & Cleopatra S. Planeta

  3. Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA

    Isabel M. Quadros & Klaus A. Miczek

  4. Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA

    Klaus A. Miczek

  5. Department of Pharmacology, Tufts University School of Medicine, Boston, MA, USA

    Klaus A. Miczek

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  1. Fabio C. Cruz
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  2. Isabel M. Quadros
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  3. Koen Hogenelst
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  4. Cleopatra S. Planeta
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  5. Klaus A. Miczek
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Correspondence to Klaus A. Miczek.

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Cruz, F.C., Quadros, I.M., Hogenelst, K. et al. Social defeat stress in rats: escalation of cocaine and “speedball” binge self-administration, but not heroin. Psychopharmacology 215, 165–175 (2011). https://doi.org/10.1007/s00213-010-2139-6

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  • DOI: https://doi.org/10.1007/s00213-010-2139-6

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