The compulsive nature of heroin abuse has been attributed to the fact that drug self-administration enables an addict to escape from and avoid the severe withdrawal symptoms resulting from opiate dependence. However, studies of incentive learning under natural motivational states suggest an alternative hypothesis, that withdrawal from heroin functions as a motivational state that enhances the incentive value of the drug, thereby enabling it to function as a much more effective reward for self-administration. In support of this hypothesis, we show here that previous experience with heroin in withdrawal is necessary for subsequent heroin-seeking behavior to be enhanced when dependent rats once again experience withdrawal.
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Koob, G. F., Stinus, L., Le Moal, M. & Bloom, F. E. Opponent process theory of motivation: neurobiological evidence from studies of opiate dependence. Neurosci. Biobehav. Revs. 13, 135–140 (1989).
Koob, G. F. Drug addiction: the yin and yang of hedonic homeostasis. Neuron 16, 893–896 (1996).
Wikler, A. Dynamics of drug dependence. Implications of a conditioning theory for research and treatment. Arch. Gen. Psychiatry 28, 611–616 (1973).
Khantzian, E. J. The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am. J. Psychiatry 142, 1259–1264 (1985).
Mucha, R. F., Gritti, M. D. & Kim, C. Aversive properties of opiate withdrawal studied in rats. NIDA Res. Monogr. 75, 567–570 (1986).
Goldberg, S. R., Hoffmeister, F., Schlichting, U. & Wuttke, W. Aversive properties of nalorphine and naloxone in morphine-dependent rhesus monkeys. J. Pharmacol. Exp. Ther. 179, 268–276 (1971).
Nader, K., Bechara, A. & van der Kooy, D. Neurobiological constraints on behavioral models of motivation. Annu. Rev. Psychol. 48, 85–114 (1997).
Dickinson, A. & Balleine, B. Motivational control of goal-directed action. Anim. Learn. Behav. 22, 1–18 (1994).
Balleine, B. Instrumental performance following a shift in primary motivation depends on incentive learning. J. Exp. Psychol. (Anim. Behav.) 18, 236–250 (1992).
Olmstead, M. C., Parkinson, J. P., Miles, F. J., Everitt, B. J. & Dickinson, A. Cocaine-seeking by rats: regulation, reinforcement and activation. Psychopharmacol. (Berl.) 152, 123–131 (2000).
Stewart, J., de Wit, H. & Eikelboom, R. Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychol. Rev. 91, 251–268 (1984).
Wise, R. A. & Bozarth, M. A. A psychomotor stimulant theory of addiction. Psychol. Rev. 94, 469–492 (1987).
Hand, T. H., Koob, G. F., Stinus, L. & Le Moal, M. Aversive properties of opiate receptor blockade: evidence for exclusively central mediation in naive and morphine-dependent rats. Brain Res. 474, 364–368 (1988).
Olmstead, M. C., Lafond, M. V., Everitt, B. J. & Dickinson, A. Cocaine-seeking by rats is a goal-directed action. Behav. Neurosci. 115, 394–402 (2001).
Ahmed, S. H., Walker, J. R. & Koob, G. F. Persistent increase in the motivation to take heroin in rats with a history of drug escalation. Neuropsychopharmacology 22, 413–421 (2000).
Bozarth, M. A. & Wise, R. A. Anatomically distinct opiate receptor fields mediate reward and physical dependence. Science 224, 516–517 (1984).
Robinson, T. E. & Berridge, K. C. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res. Rev. 18, 247–291 (1993).
Solomon, R. L. & Corbit, J. D. An opponent-process theory of motivation. I. Temporal dynamics of affect. Psychol. Rev. 81, 119–145 (1974).
Solomon, R. L. The opponent process theory of acquired motivation. Am. Psychol. 35, 691–712 (1980).
Balleine, B. W. & Dickinson, A. Goal-directed instrumental action: contingency and incentive learning and their cortical substrates. Neuropharmacology 37, 407–419 (1998).
Balleine, B. W. & Dickinson, A. The effect of lesions of the insular cortex on instrumental conditioning, evidence for a role in incentive memory. J. Neurosci. 20, 8954–8964 (2000).
Arroyo, M., Markou, A., Robbins, T. W. & Everitt, B. J. Acquisition, maintenance and reinstatement of intravenous cocaine self-administration under a second-order schedule of reinforcement in rats: effects of conditioned cues and continuous access to cocaine. Psychopharmacol. (Berl.) 140, 331–344 (1998).
Maldonado, R. et al. Inhibition of morphine withdrawal by the association of RB 101, an inhibitor of enkephalin catabolism, and the CCKB antagonist PD-134, 308. Br. J. Pharmacol. 114, 1031–1039 (1995).
This work was supported by a Medical Research Council UK Programme Grant (9537855) and was done within the MRC Cooperative for Brain, Behaviour and Neuropsychiatry. D.M.H. holds a Medical Research Council UK Training Fellowship.
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Hutcheson, D., Everitt, B., Robbins, T. et al. The role of withdrawal in heroin addiction: enhances reward or promotes avoidance?. Nat Neurosci 4, 943–947 (2001). https://doi.org/10.1038/nn0901-943
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