Skip to main content

Advertisement

SpringerLink
Log in

Effects of chronic buprenorphine treatment on levels of nucleus accumbens glutamate and on the expression of cocaine-induced behavioral sensitization in rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Chronic treatment with the mu-opioid receptor agonist, buprenorphine, reduces cocaine-induced behaviors in rats with a history of cocaine self-administration. The mechanisms underlying these actions of buprenorphine remain unclear.

Objectives

The objective of this study is to investigate the effects of chronic buprenorphine treatment on cocaine-induced activity and levels of glutamate and dopamine (DA) in the nucleus accumbens (NAc) in rats that were preexposed to cocaine or drug-naïve.

Materials and methods

In experiment 1, basal levels of NAc glutamate were assessed using in vivo microdialysis in cocaine-naïve rats that were treated chronically with buprenorphine (3.0 mg/kg per day) via osmotic minipumps or that underwent sham surgery. In experiment 2, rats were preexposed to seven daily injections of cocaine or saline. After a 12–16-day drug-free period, extracellular levels of NAc glutamate and DA and locomotor activity were assessed simultaneously, before and after an acute injection of cocaine (15 mg/kg, intraperitoneal), in rats under sham and chronic buprenorphine (3.0 mg/kg per day) treatment.

Results

Chronic buprenorphine treatment increased basal levels of glutamate in drug-naïve and cocaine-preexposed rats, blocked the expression of locomotor sensitization to cocaine, and potentiated the NAc DA response to acute cocaine in cocaine-preexposed rats.

Conclusions

These findings suggest that buprenorphine may block the expression of cocaine sensitization and other cocaine-related behaviors by increasing basal levels of glutamate in the NAc, which would serve to decrease the effectiveness of cocaine or cocaine-associated cues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Adewale AS, Platt DM, Spealman RD (2006) Pharmacological stimulation of group II metabotropic glutamate receptors reduces cocaine self-administration and cocaine-induced reinstatement of drug seeking in squirrel monkeys. J Pharmacol Exp Ther 318:922–931

    Article  PubMed  CAS  Google Scholar 

  • Baker DA, Shen H, Kalivas PW (2002a) Cystine/glutamate exchange serves as the source for extracellular glutamate: modifications by repeated cocaine administration. Amino Acids 23:161–162

    Article  PubMed  CAS  Google Scholar 

  • Baker DA, Xi ZX, Shen H, Swanson CJ, Kalivas PW (2002b) The origin and neuronal function of in vivo nonsynaptic glutamate. J Neurosci 22:9134–9141

    PubMed  CAS  Google Scholar 

  • Baker DA, McFarland K, Lake RW, Shen H, Tang XC, Toda S, Kalivas PW (2003a) Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse. Nat Neurosci 6:743–749

    Article  PubMed  CAS  Google Scholar 

  • Baker DA, McFarland K, Lake RW, Shen H, Toda S, Kalivas PW (2003b) N-acetyl cysteine-induced blockade of cocaine-induced reinstatement. Ann N Y Acad Sci 1003:349–351

    Article  PubMed  Google Scholar 

  • Baptista MA, Martin-Fardon R, Weiss F (2004) Preferential effects of the metabotropic glutamate 2/3 receptor agonist LY379268 on conditioned reinstatement versus primary reinforcement: comparison between cocaine and a potent conventional reinforcer. J Neurosci 24:4723–4727

    Article  PubMed  CAS  Google Scholar 

  • Bell K, Duffy P, Kalivas PW (2000) Context-specific enhancement of glutamate transmission by cocaine. Neuropsychopharmacology 23:335–344

    Article  PubMed  CAS  Google Scholar 

  • Boudreau AC, Wolf ME (2005) Behavioral sensitization to cocaine is associated with increased AMPA receptor surface expression in the nucleus accumbens. J Neurosci 25:9144–9151

    Article  PubMed  CAS  Google Scholar 

  • Boudreau AC, Reimers JM, Milovanovic M, Wolf ME (2007) Cell surface AMPA receptors in the rat nucleus accumbens increase during cocaine withdrawal but internalize after cocaine challenge in association with altered activation of mitogen-activated protein kinases. J Neurosci 27:10621–10635

    Article  PubMed  CAS  Google Scholar 

  • Cornish JL, Duffy P, Kalivas PW (1999) A role for nucleus accumbens glutamate transmission in the relapse to cocaine-seeking behavior. Neuroscience 93:1359–1367

    Article  PubMed  CAS  Google Scholar 

  • De Vries TJ, Schoffelmeer AN, Binnekade R, Raaso H, Vanderschuren LJ (2002) Relapse to cocaine- and heroin-seeking behavior mediated by dopamine D2 receptors is time-dependent and associated with behavioral sensitization. Neuropsychopharmacology 26:18–26

    Article  PubMed  Google Scholar 

  • Johnson RE, Eissenberg T, Stitzer ML, Strain EC, Liebson IA, Bigelow GE (1995) A placebo controlled clinical trial of buprenorphine as a treatment for opioid dependence. Drug Alcohol Depend 40:17–25

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW, Duffy P (1993) Time course of extracellular dopamine and behavioral sensitization to cocaine I. Dopamine axon terminals. J. Neurosci. 13:266–275

    PubMed  CAS  Google Scholar 

  • Kim JH, Vezina P (2002) The mGlu2/3 receptor agonist LY379268 blocks the expression of locomotor sensitization by amphetamine. Pharmacol Biochem Behav 73:333–337

    Article  PubMed  CAS  Google Scholar 

  • Kim JH, Austin JD, Tanabe L, Creekmore E, Vezina P (2005) Activation of group II mGlu receptors blocks the enhanced drug taking induced by previous exposure to amphetamine. Eur J Neurosci 21:295–300

    Article  PubMed  Google Scholar 

  • Kourrich S, Rothwell PE, Klug JR, Thomas MJ (2007) Cocaine experience controls bidirectional synaptic plasticity in the nucleus accumbens. J Neurosci 27:7921–7928

    Article  PubMed  CAS  Google Scholar 

  • LaLumiere RT, Kalivas PW (2008) Glutamate release in the nucleus accumbens core is necessary for heroin seeking. J Neurosci 28:3170–3177

    Article  PubMed  CAS  Google Scholar 

  • McFarland K, Lapish CC, Kalivas PW (2003) Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 23:3531–3537

    PubMed  CAS  Google Scholar 

  • Mello NK, Mendelson JH (1980) Buprenorphine suppresses heroin use by heroin addicts. Science 207:657–659

    Article  PubMed  CAS  Google Scholar 

  • Mello NK, Negus SS (1998) The effects of buprenorphine on self-administration of cocaine and heroin “speedball” combinations and heroin alone by rhesus monkeys. J Pharmacol Exp Ther 285:444–456

    PubMed  CAS  Google Scholar 

  • Mello NK, Bree MP, Mendelson JH (1983) Comparison of buprenorphine and methadone effects on opiate self-administration in primates. J Pharmacol Exp Ther 225:378–386

    PubMed  CAS  Google Scholar 

  • Mello NK, Mendelson JH, Bree MP, Luckas SE (1989) Buprenorphine suppresses cocaine self-administration by rhesus monkeys. Science 245:859–862

    Article  PubMed  CAS  Google Scholar 

  • Mello NK, Lukas SE, Kamien JB, Mendelson JH, Drieze J, Cone EJ (1992) The effects of chronic buprenorphine treatment on cocaine and food self-administration by rhesus monkeys. J Pharmacol Exp Ther 260:1185–1193

    PubMed  CAS  Google Scholar 

  • Montoya ID, Gorelick DA, Preston KL, Schroeder JR, Umbricht A, Cheskin LJ, Lange WR, Contoreggi C, Johnson RE, Fudala PJ (2004) Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence. Clin Pharmacol Ther 75:34–48

    Article  PubMed  CAS  Google Scholar 

  • Moran MM, McFarland K, Melendez RI, Kalivas PW, Seamans JK (2005) Cystine/glutamate exchange regulates metabotropic glutamate receptor presynaptic inhibition of excitatory transmission and vulnerability to cocaine seeking. J Neurosci 25:6389–6393

    Article  PubMed  CAS  Google Scholar 

  • Paulson PE, Robinson TE (1995) Amphetamine-induced time-dependent sensitization of dopamine neurotransmission in the dorsal and ventral striatum: a microdialysis study in behaving rats. Synapse 19:56–65

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates. Academic, London

    Google Scholar 

  • Pierce RC, Bell K, Duffy P, Kalivas PW (1996) Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization. J Neurosci 16:1550–1560

    PubMed  CAS  Google Scholar 

  • Sorge RE, Stewart J (2006a) The effects of chronic buprenorphine on intake of heroin and cocaine in rats and its effects on nucleus accumbens dopamine levels during self-administration. Psychopharmacology (Berl) 188:28–41

    Article  CAS  Google Scholar 

  • Sorge RE, Stewart J (2006b) The effects of long-term chronic buprenorphine treatment on the locomotor and nucleus accumbens dopamine response to acute heroin and cocaine in rats. Pharmacol Biochem Behav 84:300–305

    Article  PubMed  CAS  Google Scholar 

  • Sorge RE, Rajabi H, Stewart J (2005) Rats maintained chronically on buprenorphine show reduced heroin and cocaine seeking in tests of extinction and drug-induced reinstatement. Neuropsychopharmacology 30:1681–1692

    Article  PubMed  CAS  Google Scholar 

  • Spanagel R, Almeida OF, Shippenberg TS (1993) Long lasting changes in morphine-induced mesolimbic dopamine release after chronic morphine exposure. Synapse 14:243–245

    Article  PubMed  CAS  Google Scholar 

  • Sun X, Zhao Y, Wolf ME (2005) Dopamine receptor stimulation modulates AMPA receptor synaptic insertion in prefrontal cortex neurons. J Neurosci 25:7342–7351

    Article  PubMed  CAS  Google Scholar 

  • Tzschentke TM (2002) Behavioral pharmacology of buprenorphine, with a focus on preclinical models of reward and addiction. Psychopharmacology (Berl) 161:1–16

    Article  CAS  Google Scholar 

  • Ungless MA, Whistler JL, Malenka RC, Bonci A (2001) Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 411:583–587

    Article  PubMed  CAS  Google Scholar 

  • Vanderschuren LJ, Kalivas PW (2000) Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies. Psychopharmacology 151:99–120

    Article  PubMed  CAS  Google Scholar 

  • White FJ, Hu XT, Zhang XF, Wolf ME (1995) Repeated administration of cocaine or amphetamine alters neuronal responses to glutamate in the mesoaccumbens dopamine system. J Pharmacol Exp Therap 273:445–454

    CAS  Google Scholar 

  • Xi ZX, Baker DA, Shen H, Carson DS, Kalivas PW (2002) Group II metabotropic glutamate receptors modulate extracellular glutamate in the nucleus accumbens. J Pharmacol Exp Ther 300:162–1671

    Article  PubMed  CAS  Google Scholar 

  • Zhou W, Kalivas PW (2008) N-acetylcysteine reduces extinction responding and induces enduring reductions in cue- and heroin-induced drug-seeking. Biol Psychiatry 63:338–340

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Canadian Institutes of Health Research to JS and le Fonds de la recherché en santé Québec. Experimental procedures comply with the guidelines of the Canadian Council on Animal Care.

Author information

Author notes

  1. F. M. Placenza

    Present address: Department of Psychology, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario, M1C 1A4, Canada

Authors and Affiliations

  1. Center for Studies in Behavioral Neurobiology/Groupe de Recherche en Neurobiologie Comportementale, Concordia University, 7141 Sherbrooke Street West, Montreal, Quebec, H4B 1R6, Canada

    F. M. Placenza, H. Rajabi & J. Stewart

Authors
  1. F. M. Placenza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Rajabi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. M. Placenza.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Placenza, F.M., Rajabi, H. & Stewart, J. Effects of chronic buprenorphine treatment on levels of nucleus accumbens glutamate and on the expression of cocaine-induced behavioral sensitization in rats. Psychopharmacology 200, 347–355 (2008). https://doi.org/10.1007/s00213-008-1210-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-008-1210-z

Keywords

Search

Navigation