Abstract
The present study employed an animal model of drug relapse in which previously extinguished heroin self-administration behavior was reinstated following a single reinforced trial. Male albino rats were trained to traverse a straight-alley for a reinforcer consisting of a single IV injection of 0.06 mg/kg diacetylmorphine (heroin). Once the alley-running had been established, the heroin reinforcer was removed and the operant behavior permitted to extinguish over trials. On treatment day, animals were injected 45 min prior to testing with 0.0, 0.075, 0.10, 0.15 or 0.3 mg/kg of the dopamine receptor antagonist, haloperidol. A single trial was then conducted during which some animals continued to experience extinction conditions while others were injected with the heroin reinforcer upon entry into the goal box. The effects of these manipulations were determined during an additional single test trial conducted 24 h later when the subjects were no longer drugged. While heroin produced a reliable reinstatement in operant responding, this effect was dose-dependently prevented by pretreatment with haloperidol. These data suggest that dopamine receptor antagonism alters the reinforcing consequences of heroin administration as measured by heroin's ability to reinstate operant behavior following a prolonged period of nonreinforced responding.
Similar content being viewed by others
References
Ahlenius S, Engel J, Zoller M (1977) Effects of apomorphine and haloperidol on exploratory behavior and latent learning in mice. Physiol Behav 5:290–294
Bartus RT (1978) Short-term memory in the rhesus monkey: effects of dopamine blockade via acute haloperidol administration. Pharmacol Biochem Behav 9:353–357
Bechara A, Martin GM, Pridgar A, Van der Kooy D (1993) The parabrachial nucleus: a brain stem substrate critical for mediating the aversive motivational effects of morphine. Behav Neurosci 107:147–160
Bechara A, Nader K, van der Kooy D (1995) Neurobiology of withdrawal motivation: evidence for two separate aversive effects produced in morphine-naive versus morphine-dependent rats by both naloxone and spontaneous withdrawal. Behav Neurosci 109:91–105
Beninger RJ, MacLennan AJ, Pinel JPL (1980a) The use of conditioned defensive burying to test the effects of pimozide on associative learning. Pharmacol Biochem Behav 12:445–448
Beninger RJ, Mason ST, Phillips AG, Fibiger HC (1980b) The use of conditioned suppression to evaluate the nature of neuroleptic-induced avoidance deficits. J Pharmacol Exp Ther 213:623–627
Bozarth MA (1987) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin, Heidelberg, New York
Bozarth MA, Wise RA (1981) Intracranial self-administration of morphine into the ventral tegmental area of rats. Life Sci 28:551–555
Brady JV (1991) Animal models for assessing drugs of abuse. Neurosci Biobehav Rev 15:35–53
Crowley TJ (1972) The reinforcers for drug abuse: why people take drugs. Compr Psychiatry 13:51–62
de Wit H, Stewart J (1981) Reinstatement of cocaine-reinforced responding in the rat. Psychopharmacology 75:134–143
de Wit H, Stewart J (1983) Drug reinstatement of heroin-reinforced responding in the rat. Psychopharmacology 79:29–31
Duvauchelle CL, Ettenberg A (1990) Haloperidol prevents the establishment of brain stimulation induced conditioned place preferences but not aversions. Soc Neurosci Abstr 16:591
Engel J, Oreland L (1987) Brain reward systems and abuse. Raven, New York
Ettenberg A (1990) Haloperidol prevents the reinstatement of amphetamine-rewarded runway responding in rats. Pharmacol Biochem Behav 36:635–638
Ettenberg A, Geist TD (1992) Qualitative and quantitative differences in the operant runway behavior of cocaine and heroin reinforced rats. Pharmacol Biochem Behav 44:191–198
Ettenberg A, Horvitz JC (1990) Pimozide prevents the response-reinstating effects of water reinforcement in rats. Pharmacol Biochem Behav 37:465–469
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
Geist TD, Ettenberg A (1990) A simple method for studying intravenous drug reinforcement in a runway. Pharmacol Biochem Behav 36:703–706
Gerber GJ, Stretch R (1975) Drug-induced reinstatement of extinguished self-administration behavior in monkeys. Pharmacol Biochem Behav 3:1055–1061
Hall SM, Wasserman DA, Havassy BE (1991) Relapse prevention. NIDA Res Monogr 106:279–292
Harrington F, Van der Kooy D (1992) Deprivation state determines the motivational effects of neuroleptics in rats. Psychobiology 20:294–299
Himmelsbach CK (1943) Morphine, with reference to physical dependence. Fed Proc 2:201–203
Hodgson R, Rankin H, Stockwell T (1979) Alcohol dependence and the priming effect. Behav Res Ther 27:379–387
Hoffmann NG, Miller NS (1993) Perspectives of effective treatment for alcohol and drug disorders. Psychiatr Clin N Am 16:127–140
Horvitz JC, Ettenberg A (1988) Haloperidol blocks the response reinstating effects of food reward: a methodology for separating neuroleptic effects on reinforcement and motor processes. Pharmacol Biochem Behav 31:861–865
Jaffe JH, Cascella NG, Kumor KM, Sherer MA (1989) Cocaine-induced cocaine craving. Psychopharmacology 97:59–64
Koob GF (1992) Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 13:177–184
Koob GF, Bloom FE (1988) Cellular and molecular mechanisms of drug dependence. Science 242:715–723
Koob GF, Stinus L, LeMoal M, Bloom FE (1989) Opponent process theory of motivation: neurobiological evidence from studies of opiate dependence. Neurosci Biobehav Rev 13:135–140
Ludwig AM, Wikler A, Stark LH (1974) The first drink: psychobiological aspects of craving. Arch Gen Psychiatry 30:539–574
McFarland K, Ettenberg A (1995) Haloperidol differentially affects reinforcement and motivational processess in rats running an alley for intravenous heroin. Psychopharmacology 122:346–350
Mackey WB, Van der Kooy, D, (1985) Neuroleptics block the positive reinforcing effects of amphetamine but not of morphine as measured by place conditioning. Pharmacol Biochem Behav 22:101–105
Marlatt A, Gordon J (1985) Relapse prevention. Guilford, New York
Nader K, Bechara A, Roberts DCS, van der Kooy D (1994) Neuroleptics block high- but not low-dose heroin place preferences: further evidence for a two-system model of motivation. Behav Neurosci 108:1128–1138
O'Brien CP, Childress AR, McLellan AT (1991) Conditioning factors may help to understand and prevent relapse in patients who are recovering from dependence. NIDA Res Monogr 106:293–312
Pettit HO, Ettenberg A, Bloom FE, Koob GF (1984) Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats. Psychopharmacology 84:167–173
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
Satel SL, Kosten TR, Schuckit MA, Fischman MW (1993) Should protracted withdrawal from drugs be included in the DSM-IV? Am J Psychiatry 150:695–704
Schuster CR, Thompson T (1969) Self-administration of and behavioral dependence on drugs. Annu Rev Pharmacol 9:483–502
Shoaib M, Spanagel R (1994) Mesolimbic sites mediate the discriminativge stimulus effects of morphine. Eur J Pharmacol 252:69–75
Slikker W, Brocco MJ, Killam KF (1984) Reinstatement of responding maintained by cocaine or thiamylal. J Pharmacol Exp Ther 228:43–52
Smith SG, Davis WM (1973) Haloperidol effects on morphine self-administration: testing for pharmacological modification of the primary reinforcement mechanism. Psychol Rec 23:215–221
Solomon RL, Corbit JD (1974) An opponent-process theory of motivation. I. Temporal dynamics of affect. Psychol Rev 81:119–145
Spyraki C, Fibiger HC, Phillips AG (1983) Attenuation of heroin reward in rats by disruption of the mesolimbic dopamine system. Psychopharmacology 79:278–283
Stewart J (1984) Reinstatement of heroin and cocaine self-administration behavior in the rat by intracerebral application of morphine in the ventral tegmental area. Pharmacol Biochem Behav 20:917–923
Stewart J, Wise RA (1992) Reinstatement of heroin self-administration habits: morphine prompts and naltrexone discourages renewed responding after extinction. Psychopharmacology 108:79–84
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 91:251–268
Stretch R, Gerber GJ (1973) Drug-induced reinstatement of amphetamine self-administration in monkeys. Can J Psychol 27:168–177
Tobena A, Fernandez-Teruel A, Escorihuela RM, Nunez JF, Zapata A, Ferre P, Sanchez R (1993) Limits of habituation and extinction: implications for relapse prevention programs in addictions. Drug Alcohol Depend 32:209–217
Wise RA (1987) Intravenous drug self-administration: a special case of positive reinforcement. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin, Heidelberg, New York, pp 117–141
Wise RA, Murray A, Bozarth MA (1990) Bromocriptine self-administration and bromocriptine-reinstatement of cocaine-trained and heroin-trained lever-pressing in rats. Psychopharmacology 100:355–360
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ettenberg, A., MacConell, L.A. & Geist, T.D. Effects of haloperidol in a response-reinstatement model of heroin relapse. Psychopharmacology 124, 205–210 (1996). https://doi.org/10.1007/BF02246658
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02246658