Abstract
Endogenous opioid systems have been implicated in experimental cocaine addiction. One aspect of this involvement may be the modulation of the motivational properties of cocaine by endogenous opioids. The present study assessed the effect of opioid blockade with naloxone (NLX) on cocaine's motivational properties using the conditioned place preference procedure. Treatment with doses of NLX that did not induce place aversion (0.01–1.0 mg/kg−1, SC), dose-dependently attenuated place preference induced by cocaine (10 or 20 mg/kg−1, IP). This effect of NLX was present when administered during acquisition of cocaine-induced place preference and when administered before expression of cocaine's motivational effects. These data support the notion that the (conditioned) motivational properties of cocaine are modulated through activation of opioid systems by endogenous opioid peptides. Furthermore, it is suggested that an interaction between endogenous opioid systems and dopaminergic systems in the brain might be of importance in the motivational facilitation of experimental cocaine addiction.
Similar content being viewed by others
References
Bain GT, Kornetsky C (1986) Naloxone attenuation of the effect of cocaine on rewarding brain stimulation. Life Sci 40:1119–1125
Beninger RJ (1983) The role of dopamine in locomotor activity and learning. Brain Res Rev 6:173–196
Bilsky EJ, Montegut MJ, Delong CL, Reid LD (1992) Opioidergic modulation of conditioned place preference. Life Sci 50:PL85-PL90
Blackburn JR, Phillips AG, Fibiger HC (1987) Dopamine and preparatory behavior: I effects of pimozide. Behav Neurosci 10:325–360
Bozarth MA, Wise A (1981) Intracranial self-administration of morphine into the ventral tegmental area in rats. Life Sci 28:551–555
Britton DR, Curzon P, Mackenzie RG, Kebabian JW, Williams JEG, Kerkman D (1991) Evidence for involvement of both D1 and D2 receptors in maintaining cocaine self-administration. Pharmacol Biochem Behav 39:911–915
Carey MP, Ross JA, Enns MP (1981) Naloxone suppresses feeding and drinking but not wheel running behavior in rats. Pharmacol Biochem Behav 14:569–571
Carroll ME, Lac St, Walker ST, Kragh MJ, Newman T (1986) Effects of naltrexone on intravenous cocaine self-administration in rats during food satiation and deprivation. J Pharmacol Exp Ther 238:1–7
Corrigall WA, Coen KM (1991a) Cocaine self-administration is increased by both D1 and D2 dopamine antagonists. Pharmacol Biochem Behav 39:799–802
Corrigall WA, Coen KM (1991b) Opiate antagonists reduce cocaine but not nicotine self-administration. Psychopharmacology 104:167–170
De Vry J, Donselaar I, Van Ree JM (1989) Food deprivation and acquisition of cocaine self-administration in rats: effect of naltrexone and haloperidol. J Pharmacol Exp Ther 251:735–740
Di Chiara G, Acquas E, Carboni E (1992) Drug motivation and abuse: a neurobiological perspective. In: Kalivas PW, Samson HH (eds) The neurobiology of drug and alcohol addiction. Ann NY Acad Sci 654:207–219
Devine DP, Leone P, Pocock D, Wise RA (1993) Differential involvement of ventral tegmental mu, delta and kappa opioid receptors in the modulation of basal mesolimbic dopamine release. J Pharmacol Exp Ther 266:1236–1246
Dum J, Herz A (1984) Endorphinergic modulation of neural reward systems indicated by behavioral changes. Pharmacol Biochem Behav 21:259–266
Dum J, Gramsch CH, Herz A (1983) Activation of hypothalamicβ-endorphin pools by reward induced by highly palatable food. Pharmacol Biochem Behav 18:443–447
Ettenberg A, Pettit HO, Bloom FE, Koob GF (1982) Heroin and cocaine intravenous self-administration in rats: mediation by separate neural systems. Psychopharmacology 78:204–209
File SE (1980) Naloxone reduces social and exploratory activity in the rat. Psychopharmacology 71:41–44
Heikkila RE, Orlansky H, Cohen G (1975) Studies on the distinction between uptake inhibition and release of [3H]dopamine in rat brain tissue slices. Biochem Pharmacol 24:847–852
Houdi AA, Bardo TB, Van Loon GL (1989) Opioid mediation of cocaine-induced hyperactivity and reinforcement. Brain Res 497:195–198
Jaffe JH, Martin WR (1990) Opioid analgesics and antagonists. In: Goodman and Gilman A, Rall TW, Nies AS, Taylor P (eds) The pharmacological basis of therapeutics. Pergamon Press, New York, pp 485–525
Kalivas PW, Abhold R (1987) Enkephalin release into the ventral tegmental area in response to stress: modulation of mesocorticolimbic dopamine. Brain Res 414:339–348
Klitenick MA, DeWitte P, Kalivas PW (1992) Regulation of somatodendritic dopamine release in the ventral tegmental area by opioids and GABA: an in vivo microdialysis study. J Neurosci 12:2623–2632
Kosterlitz HW, Watl AJ (1968) Kinetic parameters of narcotic antagonists, with particular reference toN-allylnoroxymorphine (naloxone). Br J Pharmacol 33:266–276
Mello NK, Mendelson JH, Bree MP, Lukas SE (1990) Buprenorphine and naltrexone effects on cocaine self-administration by rhesus monkeys. J Pharmacol Exp Ther 254:926–939
Menkens K, Bilsky EJ, Wild KD, Portoghese PS, Reid LD, Porreca F (1992) Cocaine place preference is blocked byδ-opioid receptor antagonist, naltrindole. Eur J Pharmacol 219:345–346
Morency MA, Beninger RJ (1986) Dopaminergic substrates of cocaine-induced place conditioning. Brain Res 399:33–41
Mucha RF, Iversen SD (1984) Reinforcing properties of morphine and naloxone revealed by conditioned place preference: a procedural examination. Psychopharmacology 82:241–247
Mucha RF, Van der Kooy D, O'Shaughnessy M, Bucenieks P (1982) Drug reinforcement studied by the use of place conditioning in rat. Brain Res 243:91–105
Pfaus JG, Phillips AG (1991) Role of dopamine in anticipatory and consummatory aspects of sexual behavior. Behav Neurosci 105:727–743
Ramsey NF (1991) Cocaine dependence; factors in the initiation of self-administration in rats. Thesis, Utrecht University
Reid LD, Hubbell CL, Glaccum MB, Bilsky EJ, Portoghese PS, Porreca F (1993) Naltrindole, an opioid delta receptor antagonist, blocks cocaine-induced facilitation of responding for rewarding brain stimulation. Life Sci 52:PL 67–71
Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ (1987) Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237:1219–1223
Roberts DCS, Koob GF (1982) Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats. Pharmacol Biochem Behav 17:901–904
Roberts DCS, Corcoran ME, Fibiger HC (1977) On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine. Pharmacol Biochem Behav 6:615–620
Roberts DCS, Koob GF, Klonoff P, Fibiger HC (1980) Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 12:781–787
Rodgers RJ, Deacon MJ (1979) Effect of naloxone on the behaviour of rats exposed to a novel environment. Psychopharmacology 65:103–105
Schenk S, Horger BA, Peltier R, Shelton K (1991) Supersensitivity to the reinforcing effects of cocaine following 6-hydroxydopamine lesions to the medial prefrontal cortex. Brain Res 543:227–235
Spanagel R, Herz A, Shippenberg TS (1992) Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci USA 89:2046–2050
Spyraki C, Fibiger HC, Phillips AG (1982) Cocaine-induced place preference conditioning: lack of effects of neuroleptics and 6-hydroxydopamine lesions. Brain Res 253:195–203
Stewart J, De Wit H, Eikelboom R (1984) Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychol Rev 2:251–268
Suzuki T, Shiozaki Y, Masukawa Y, Misawa M, Nagase H (1992) The role of mu- and kappa-opioid receptors in cocaine-induced conditioned place preference. Jpn J Pharmacol 58:435–442
Suzuki T, Mori T, Tsuij M, Misawa M, Nagase H (1994) The role ofδ-opioid receptor subtypes in cocaine- and metamphetamine-induced place preferences. Life Sci 55:PL339–344
Van Ree JM (1979) Reinforcing stimulus properties of drugs. Neuropharmacology 18:963–969
Walker JM, Berntson GG, Paulucci TS, Champney TC (1981) Blockade of endogenous opiates reduces activity in the rat. Pharmacol Biochem Behav 14:113–116
Willner P, Scheel-Krüger J (1991) The mesolimbic dopamine system: from motivation to action. Wiley Chichester
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gerrits, M.A.F.M., van Ree, J.M., Patkina, N. et al. Opioid blockade attenuates acquisition and expression of cocaine-induced place preference conditioning in rats. Psychopharmacology 119, 92–98 (1995). https://doi.org/10.1007/BF02246059
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02246059