Abstract
It is commonly believed that repeated exposures diminish the pleasurable effects of drugs and hence that pleasure must have only a minor role in addiction. In six experiments with rats, repeated exposures to amphetamine, morphine, or cocaine were found to enhance the drug-induced rewarding effect as measured by conditioned place preference. Thus, sensitization to the rewarding effect, rather than tolerance, was obtained. Also, cross-sensitization was obtained; exposures to amphetamine enhanced the rewarding effect of morphine and vice versa; similarly, exposures to morphine enhanced the rewarding effect of cocaine. These findings support a new theory: drugs of abuse are addictive because repeated exposures sensitize the central reward mechanism so that drug taking produces a progressively greater reinforcing effect each time it occurs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bozarth MA (1986) Neural basis of psychomotor stimulant and opiate reward: evidence suggesting the involvement of a common dopaminergic system. Behav Brain Res 22:107–116
Braveman NS (1975) Formation of taste aversions in rats following prior exposure to sickness. Learn Motiv 6:512–534
Falk JL, Dews PB, Schuster CR (1983) Commonalities in the environmental control of behavior. In: Levison PK, Gerstein DR, Maloff DR (eds) Commonalities in substance abuse and habitual behavior. DC Heath, Lexington, MASS, pp 47–110
Ford KA, Riley AL (1984) The effects of LiCl preexposures on amphetamine-induced taste aversions: an assessment of blocking. Pharmacol Biochem Behav 20:643–645
Goudie AJ, Dickins DW, Thornton EW (1978) Cocaine-induced taste aversions in rats. Pharmacol Biochem Behav 8:757–761
Haertzen CA, Hooks NT (1969) Changes in personality and subjective experience associated with the chronic administration and withdrawal of opiates. J Nerv Ment Dis 140:606–614
Joyce EM, Iversen SD (1979) The effect of morphine applied locally to mesencephalic dopamine cell bodies on spontaneous motor activity in the rat. Neurosci Lett 14:207–212
Joyce EM, Koob GF (1981) Amphetamine-, scopolamine-, and caffeine-induced locomotor activity following 6-hydroxydopamine lesions of the mesolimbic dopamine system. Psychopharmacology 73:311–313
Kalivas PW (1985) Sensitization to repeated enkephalin administration into the ventral tegmental area of the rat. II. Involvement of the mesolimbic dopamine system. J Pharmacol Exp Ther 235:544–550
Kamin LJ (1969) Predictability, surprise, attention, and conditioning. In: Campbell BA, Church RM (eds) Punishment and aversive behavior. Appleton-Century-Crofts, New York, pp 279–296
Kilbey MM, Ellinwood EH (1977) Chronic administration of stimulant drugs: Response modification. In: Ellinwood EH, Kilbey MM (eds) Cocaine and other stimulants. Plenum Press, New York, pp 409–429
Lett BT (1988) Enhancement of conditioned preference for a place paired with amphetamine produced by blocking the association between place and amphetamine-induced sickness. Psychopharmacology 95:390–394
Lindesmith A (1968) Addiction and opiates, 2nd edn. Aldine Chicago
McAuliffe WE, Gordon RA (1974) A test of Lindesmith's theory of addiction: the frequency of euphoria among long-term addicts. Am J Sociol 79:795–840
Mucha RF, Herz A (1985) Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning. Psychopharmacology 86:274–280
Mucha RF, Iversen SD (1984) Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination. Psychopharmacology 82:241–247
Mucha RF, van der Kooy D, O'Shaughnessy M, Bucenieks P (1982) Drug reinforcement studied by use of place conditioning in rat. Brain Res 243:91–105
Phillips AG, Broekkamp CL, Fibiger HC (1983) Strategies for studying the neurochemical substrates of drug reinforcement in rodents. Prog Neuropsychopharmacol Biol Psychol 7:585–590
Reicher MA, Holman EW (1977) Location preference and flavor aversion reinforced by amphetamine in rats. Anim Learn Behav 5:343–346
Riley AL, Jacobs WJ, LoLordo VM (1978) Morphine-induced taste aversions: a consideration of parameters. Physiol Psychol 6:96–100
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
Robinson TE, Becker JB (1986) Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res Rev 11:157–198
Segal DS, Mandell AJ (1974) Long-term administration of amphetamine: progressive augmentation of motor activity and stereotypy. Pharmacol Biochem Behav 2:249–255
Spyraki C, Fibiger HC, Phillips AG (1982a) Cocaine-induced place preference conditioning: lack of effects of neuroleptics and 6-hydroxydopamine lesions. Brain Res 253:195–203
Spyraki C, Fibiger HC, Phillips AG (1982b) Dopaminergic substrates of amphetamine-induced place preference conditioning. Brain Res 253:185–193
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, Vezina P (1987) Environment-specific enhancement of the hyperactivity induced by systemic or intra-VTA morphine injections in rats pre-exposed to amphetamine. Psychobiology 15:144–153
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
Vezina P, Stewart J (1984) Conditioning and place-specific sensitization of increases in activity induced by morphine in the VTA. Pharmacol Biochem Behav 20:925–934
Vogel JR, Nathan BA (1976) Reduction of learned taste aversion by pre-exposure to drugs. Psychopharmacology 44:167–172
Wikler A (1973) Dynamics of drug dependence: implications of a conditioning theory for research and treatment. In: Fisher S, Freedman AM (eds) Opiate addiction: origins and treatment. VH Winston, Washington, DC, pp 7–21
Wise RA (1978) Catecholamine theories of reward: a critical review. Brain Res 152:215–247
Wise RA (1987) The role of reward pathways in the development of drug dependence. Pharmacol Ther 35:227–263
Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94:469–492
Woolverton WL, Cervo L, Johanson CE (1984) Effects of repeated methamphetamine administrations on methamphetamine self-administration in rhesus monkeys. Pharmacol Biochem Behav 21:737–741
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lett, B.T. Repeated exposures intensify rather than diminish the rewarding effects of amphetamine, morphine, and cocaine. Psychopharmacology 98, 357–362 (1989). https://doi.org/10.1007/BF00451687
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00451687