Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

The role of withdrawal in heroin addiction: enhances reward or promotes avoidance?

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The influence of drug dose and time out on heroin-seeking activity.
Figure 2: Incentive learning study.
Figure 3: Effect of previous heroin experience on heroin-seeking activity.

Similar content being viewed by others

References

  1. 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).

    Article  CAS  Google Scholar 

  2. Koob, G. F. Drug addiction: the yin and yang of hedonic homeostasis. Neuron 16, 893–896 (1996).

    Article  CAS  Google Scholar 

  3. Wikler, A. Dynamics of drug dependence. Implications of a conditioning theory for research and treatment. Arch. Gen. Psychiatry 28, 611–616 (1973).

    Article  CAS  Google Scholar 

  4. Khantzian, E. J. The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am. J. Psychiatry 142, 1259–1264 (1985).

    Article  CAS  Google Scholar 

  5. Mucha, R. F., Gritti, M. D. & Kim, C. Aversive properties of opiate withdrawal studied in rats. NIDA Res. Monogr. 75, 567–570 (1986).

    CAS  PubMed  Google Scholar 

  6. 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).

    CAS  PubMed  Google Scholar 

  7. Nader, K., Bechara, A. & van der Kooy, D. Neurobiological constraints on behavioral models of motivation. Annu. Rev. Psychol. 48, 85–114 (1997).

    Article  CAS  Google Scholar 

  8. Dickinson, A. & Balleine, B. Motivational control of goal-directed action. Anim. Learn. Behav. 22, 1–18 (1994).

    Article  Google Scholar 

  9. Balleine, B. Instrumental performance following a shift in primary motivation depends on incentive learning. J. Exp. Psychol. (Anim. Behav.) 18, 236–250 (1992).

    Article  CAS  Google Scholar 

  10. 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).

    Article  CAS  Google Scholar 

  11. 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).

    Article  CAS  Google Scholar 

  12. Wise, R. A. & Bozarth, M. A. A psychomotor stimulant theory of addiction. Psychol. Rev. 94, 469–492 (1987).

    Article  CAS  Google Scholar 

  13. 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).

    Article  CAS  Google Scholar 

  14. 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).

    Article  CAS  Google Scholar 

  15. 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).

    Article  CAS  Google Scholar 

  16. Bozarth, M. A. & Wise, R. A. Anatomically distinct opiate receptor fields mediate reward and physical dependence. Science 224, 516–517 (1984).

    Article  CAS  Google Scholar 

  17. 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).

    Article  CAS  Google Scholar 

  18. Solomon, R. L. & Corbit, J. D. An opponent-process theory of motivation. I. Temporal dynamics of affect. Psychol. Rev. 81, 119–145 (1974).

    Article  CAS  Google Scholar 

  19. Solomon, R. L. The opponent process theory of acquired motivation. Am. Psychol. 35, 691–712 (1980).

    Article  CAS  Google Scholar 

  20. Balleine, B. W. & Dickinson, A. Goal-directed instrumental action: contingency and incentive learning and their cortical substrates. Neuropharmacology 37, 407–419 (1998).

    Article  CAS  Google Scholar 

  21. 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).

    Article  CAS  Google Scholar 

  22. 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).

    Article  CAS  Google Scholar 

  23. 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).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. M. Hutcheson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn0901-943

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing