Psychopharmacology

, Volume 200, Issue 1, pp 59–70

Stress-induced reinstatement of cocaine seeking is mediated by the kappa opioid system

Original Investigation

Abstract

Introduction

Prior activation of the kappa opioid system by repeated stress or agonist administration has been previously shown to potentiate the rewarding properties of subsequently administered cocaine. In the present study, intermittent and uncontrollable footshock, a single session of forced swim, or acute administration of the kappa agonist U50,488 (5 mg/kg) were found to reinstate place preference in mice previously conditioned with cocaine (15 mg/kg) and subsequently extinguished by repeated training sessions without drug.

Results and discussion

Stress-induced reinstatement did not occur for mice pretreated with the kappa opioid receptor antagonist norbinaltorphimine (10 mg/kg) and did not occur in mice lacking either kappa opioid receptors (KOR −/−) or prodynorphin (Dyn −/−). In contrast, the initial cocaine conditioning and extinction rates were not significantly affected by disruption of the kappa opioid system. Cocaine-injection also reinstated conditioned place preference in extinguished mice; however, cocaine-primed reinstatement was not blocked by kappa opioid system disruption.

Conclusion

The results suggest that stress-induced drug craving in mice may require activation of the dynorphin/kappa opioid system.

Keywords

Cocaine Reinstatement Stress Dynorphin Kappa receptor antagonist 

Abbreviations

norBNI

norbinaltorphimine

CPP

conditioned place preference

HSD

Tukey honestly significant difference

KOR

kappa opioid peptide receptor

Dyn−/−

prodynorphin gene knockout mice

References

  1. Beardsley PM, Howard JL, Shelton KL, Carroll FI (2005) Differential effects of the novel kappa opioid receptor antagonist, JDTic on reinstatement of cocaine-seeking induced by footshock stressors vs. cocaine primes and its antidepressant-like effects in rats. Psychopharmacology 183:118–126PubMedCrossRefGoogle Scholar
  2. Bardo MT, Rowlett JK, Harris MJ (1995) Conditioned place preference using opiate and stimulant drugs: a meta-analysis. Neurosci Biobehav Rev 19:39–51PubMedCrossRefGoogle Scholar
  3. Bossert JM, Ghitza UE, Lu L, Epstein DH, Shaham Y (2005) Neurobiology of relapse to heroin and cocaine seeking: an update and clinical implications. Eur J Pharmacol 526:36–50PubMedCrossRefGoogle Scholar
  4. Carey AN, Borozny K, Aldrich JV, McLaughlin JP (2007) Reinstatement of cocaine place-conditioning prevented by the peptide kappa-opioid receptor antagonist arodyn. Eur J Pharmacol 569:84–89PubMedCrossRefGoogle Scholar
  5. Carlezon WA, Duman RS, Nestler EJ (2005) The many faces of CREB. Trends Neurosci 28:436–445PubMedCrossRefGoogle Scholar
  6. Chefer VI, Czyzyk T, Bolan EA, Moron J, Pintar JE, Shippenberg TS (2005) Endogenous kappa-opioid receptor systems regulate mesoaccumbal dopamine dynamics and vulnerability to cocaine. J Neurosci 25:5029–5037PubMedCrossRefGoogle Scholar
  7. Cioccociopo R, Martin-Fardon R, Weiss F (2002) Effect of selective blockade of m1 or d opioid receptors on reinstatement of alcohol-seeking behavior by drug-associated stimuli in rats. Neuropsychopharmacology 27:391–399CrossRefGoogle Scholar
  8. Covington HE, Miczek KA (2005) Intense cocaine self-administration after episodic social defeat stress, but not after aggressive behavior: dissociation from corticosterone activation. Psychopharmacology 183:331–340PubMedCrossRefGoogle Scholar
  9. Crawford CA, McDougall SA, Bolanos CA, Hall S, Berger SP (1995) The effects of the kappa-opioid agonist, U50,488 on cocaine-induced conditioned and unconditioned behaviors and Fos immunoreactivity. Psychopharmacology 120:392–399PubMedCrossRefGoogle Scholar
  10. 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 85:5274–5278PubMedCrossRefGoogle Scholar
  11. De Wit H, Stewart J (1981) Drug reinstatement of cocaine-reinforced responding in the rat. Psychopharmacology 75:134–143PubMedCrossRefGoogle Scholar
  12. De Wit H, Stewart J (1983) Drug reinstatement of heroin-reinforced responding in the rat. Psychopharmacology 79:29–31PubMedCrossRefGoogle Scholar
  13. Epstein DH, Preston KL, Stewart J, Shaham Y (2006) Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology 189:1–16PubMedCrossRefGoogle Scholar
  14. Erb S, Stewart J (1999) A role for the bed nucleus of the stria terminalis, but not the amygdala, in the effects of corticotrophin-releasing factor on stress-induced reinstatement of cocaine seeking. J Neurosci 19:RC35PubMedGoogle Scholar
  15. Erb S, Shaham Y, Stewart J (1996) Stress reinstates cocaine-seeking behavior after prolonged extinction and a drug-free period. Psychopharmacology 128:408–412PubMedCrossRefGoogle Scholar
  16. Erb S, Shaham Y, Stewart J (1998) The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats. J Neurosci 18:5529–5536PubMedGoogle Scholar
  17. Erb S, Hitchcott PK, Rajabi H, Mueller D, Shaham Y, Stewart J (2000) Alpha-2 adrenoreceptor agonists block stress-induced reinstatement of cocaine seeking. Neuropsychopharmacology 23:138–150PubMedCrossRefGoogle Scholar
  18. Erb S, Salamaso N, Rodaros D, Stewart J (2001) A role for the CRF-containing pathway from the central nucleus of the amygdala to the bed nucleus of the stria terminalis in the stress-induced reinstatement of cocaine seeking in rats. Psychopharmacology 158:360–365PubMedCrossRefGoogle Scholar
  19. Gerber GJ, Stretch R (1975) Drug-induced reinstatement of extinguished self-administration behavior in monkeys. Pharmacol Biochem Behav 3:1055–1061PubMedCrossRefGoogle Scholar
  20. Glick SD, Maisonnueve IM, Raucci J, Archer S (1995) Kappa-opioid inhibition of morphine and cocaine self-administration in rats. Brain Res 681:147–152PubMedCrossRefGoogle Scholar
  21. Katz JL, Higgins ST (2003) The validity of the reinstatement model of craving and relapse to drug use. Psychopharmacology 168:21–30PubMedCrossRefGoogle Scholar
  22. Koob GF (2006) The neurobiology of addiction: a neuroadaptational view relevant for diagnosis. Addiction 101(Suppl 1):23–30PubMedCrossRefGoogle Scholar
  23. Kreibich AS, Blendy JA (2004) cAMP response element-binding protein is required for stress but not cocaine-induced reinstatement. J Neurosci 24:6686–6692PubMedCrossRefGoogle Scholar
  24. Land BB, Bruchas MR, Lemos JC, Xu M, Melief EJ, Chavkin C (2008) The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system. J Neurosci 28:407–414PubMedCrossRefGoogle Scholar
  25. Le AD, Poulos CX, Harding S, Watchus J, Juzytsch W, Shaham Y (1999) Effects of naltrexone and fluoxetine on alcohol self-administration and reinstatement of alcohol seeking induced by priming injections of alcohol and exposure to stress. Neuropsychopharmacology 21:435–444PubMedCrossRefGoogle Scholar
  26. Lee B, Tiefenbacher S, Platt DM, Spealman RD (2004) Pharmacological blockade of a2-adrenoreceptors induces reinstatement of cocaine-seeking behavior in Squirrel monkeys. Neuropsychopharmacology 29:686–693PubMedCrossRefGoogle Scholar
  27. Leri F, Flores J, Rodaros D, Stewart J (2002) Blockade of stress-induced but not cocaine-induced reinstatement by infusion of noradrenergic antagonists into the bed nucleus of the stria terminalis or the central nucleus of the amygdala. J Neurosci 22:5713–5718PubMedGoogle Scholar
  28. Leshner AI (1997) Addiction is a brain disease, and it matters. Science 278:45–47PubMedCrossRefGoogle Scholar
  29. Martin-Fardon R, Ciccocioppo R, Mass M, Weiss F (2000) Nociception prevents stress-induced ethanol- but not cocaine seeking behavior in rats. Neuroreport 11:1939–1943PubMedCrossRefGoogle Scholar
  30. McLaughlin JP, Marton-Popovici M, Chavkin C (2003) κ Opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses. J Neurosci 23:5674–5683PubMedGoogle Scholar
  31. McLaughlin JP, Land BB, Li S, Pintar JE, Chavkin C (2006a) Prior activation of kappa opioid receptors by U50,488 mimics repeated forced swim stress to potentiate cocaine place preference conditioning. Neuropharmacology 31:787–794Google Scholar
  32. McLaughlin JP, Li S, Valdez J, Chavkin TA, Chavkin C (2006b) Social defeat stress-induced behavioral responses are mediated by the endogenous kappa opioid system. Neuropsychopharmacology 31:1241–1248PubMedCrossRefGoogle Scholar
  33. Mello NK, Negus SS (1998) Effects of kappa opioid agonists on cocaine- and food-maintained responding by Rhesus monkeys. J Pharmacol Exp Ther 286:812–824PubMedGoogle Scholar
  34. Mueller D, Stewart J (2000) Cocaine-induced conditioned place preference: reinstatement by priming injections of cocaine after extinction. Behav Brain Res 115:39–47PubMedCrossRefGoogle Scholar
  35. Negus SS (2004) Effects of the kappa opioid agonist U50,488 and the kappa opioid antagonist nor-binaltorphimine on choice between cocaine and food in rhesus monkeys. Psychopharmacology 176:204–213PubMedCrossRefGoogle Scholar
  36. Negus SS, Mello NK, Portoghese PS, Lin CE (1997) Effects of kappa opioids on cocaine self-administration by Rhesus monkeys. J Pharmacol Exp Ther 282:44–55PubMedGoogle Scholar
  37. Nikolarakis KE, Almeida OF, Herz A (1987) Feedback inhibition of opioid peptide release in the hypothalamus of the rat. Neuroscience 23:143–148PubMedCrossRefGoogle Scholar
  38. Overton JM, Fisher LA (1989) Modulation of central nervous system actions of corticotrophin-releasing factor by dynorphin-related peptides. Brain Res 488:233–240PubMedCrossRefGoogle Scholar
  39. Pfeiffer A, Brantl V, Herz A, Emrich HM (1986) Psychotomimesis mediated by kappa opiate receptors. Science 233:774–776PubMedCrossRefGoogle Scholar
  40. Ribeiro Do Couto B, Aguilar MA, Manzanedo C, Rodriguez-Arias M, Armario A, Miňarro J (2006) Social stress is as effective as physical stress in reinstating morphine-induced place preference in mice. Psychopharmacology 185:459–470PubMedCrossRefGoogle Scholar
  41. Roth KA, Weber E, Borchas JD, Chang D, Chang JK (1983) Immunoreactive dynorphin-(1-8) and corticotrophin-releasing factor in subpopulation of hypothalamic neurons. Science 219:189–191PubMedCrossRefGoogle Scholar
  42. Schenk S, Partridge B, Shippenberg TS (1999) U69593, a kappa-opioid agonist, decreases cocaine self-administration and decreases cocaine-produced drug-seeking. Psychopharmacology 144:339–346PubMedCrossRefGoogle Scholar
  43. Schenk S, Partridge B, Shippenberg TS (2000) Reinstatement of extinguished drug-taking behavior in rats: effect of the kappa-opioid receptor agonist, U69593. Psychopharmacology 151:85–90PubMedCrossRefGoogle Scholar
  44. Shaham Y, Stewart J (1996) Effects of opioid and dopamine receptor antagonists on relapse induced by stress and reexposure to heroin in rats. Psychopharmacology 125:385–391PubMedCrossRefGoogle Scholar
  45. Shaham Y, Rajabi H, Stewart J (1996) Relapse to heroin-seeking in rats under opioid maintenance: the effects of stress, heroin priming, and withdrawal. J Neurosci 16:1957–1963PubMedGoogle Scholar
  46. Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology 168:3–20PubMedCrossRefGoogle Scholar
  47. Shalev U, Highfield D, Yap J, Shaham Y (2000) Stress and relapse to drug seeking in rats: studies on the generality of the effect. Psychopharmacology 150:337–346PubMedCrossRefGoogle Scholar
  48. Shippenberg TS, Herz A (1986) Differential effects of mu and kappa opioid systems on motivational processes. NIDA Res Monogr 75:563–566PubMedGoogle Scholar
  49. Shippenberg TS, LeFevour A, Heidbreder C (1996) kappa-Opioid receptor agonists prevent sensitization to the conditioned rewarding effects of cocaine. J Pharmacol Exp Ther 276:545–554PubMedGoogle Scholar
  50. Shippenberg TS, Zapata A, Chefer VI (2007) Dynorphin and the pathophysiology of drug addiction. Pharmacol Ther 116:306–321PubMedCrossRefGoogle Scholar
  51. Sirinathsinghji DJS, Nikolarakis KE, Herz A (1989) Corticotropin-releasing factor stimulates the release of methionine-enkephalin and dynorphin from the neostriatum and globus pallidus of the rat: in vitro and in vivo studies. Brain Res 490:276–291PubMedCrossRefGoogle Scholar
  52. Song M, Wang XY, Zhao M, Wang XY, Zhai HF, Lu L (2007) Role of stress in acquisition of alcohol-conditioned place preference in adolescent and adult mice. Alcohol Clin Exp Res 31:2001–2005PubMedCrossRefGoogle Scholar
  53. Stewart J (2003) Stress and relapse to drug seeking: studies in laboratory animals shed light on mechanisms and sources of long-term vulnerability. Am J Addict 12:1–17PubMedCrossRefGoogle Scholar
  54. Stretch R, Gerber GJ (1973) Drug-induced reinstatement of amphetamine self-administration behaviour in monkeys. Can J Psychol 27:168–177PubMedGoogle Scholar
  55. Valdez GR, Platt DM, Rowlett JK, Ruedi-Bettschen D, Spealman RD (2007) Κ agonist-induced reinstatement of cocaine seeking in squirrel monkeys: a role for opioid and stress-related mechanisms. J Pharmacol Exp Ther 323:525–533PubMedCrossRefGoogle Scholar
  56. Walsh SL, Geter-Douglas B, Strain EC, Bigelow GE (2001) Enadoline and butorphanol: evaluation of k-agonists on cocaine pharmacodynamics and cocaine self-administration in humans. J Pharmacol Exp Ther 299:147–158PubMedGoogle Scholar
  57. Wang B, Luo F, Zhang WT, Han JS (2000) Stress or drug priming induces reinstatement of extinguished conditioned place preference. Neuroreport 11:2781–2784PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of PharmacologyUniversity of WashingtonSeattleUSA

Personalised recommendations