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Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function

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An Erratum to this article was published on 08 December 2011

Abstract

Rationale

The transition from initial drug use to drug addiction has been proposed to result from an allostatic decrease in reward function driven by an overactivation of brain antireward processes.

Objectives

How decreased reward function explains compulsive drug use is not entirely clear at present, and is still a subject for debate.

Methods

We present a quantitative model of cocaine self-administration that integrates pharmacokinetic, pharmacodynamic, and motivational factors to address this question. The model assumes that reward system responsivity is a homeostatically regulated process where the desired level of responsivity (called the reward set point) is initially different from the baseline level. The reduction or correction of this difference or error in reward function would drive cocaine self-administration.

Results

Theoretical data obtained by computer simulation fit the experimental data obtained in animals self-administering cocaine (i.e., the within-session pattern of self-injections, the shape and curvature of the dose-injection function, the nonlinear relationship between drug intake and regulated drug effects). Importantly, simulation of an allostatic decrease in reward system responsivity exacerbates the initial error that drives self-administration, thereby increasing both the intake of, and the motivation for, the drug. This allostatic change manifests as a vertical shift in the dose-injection function similar to that seen in animals with escalating cocaine self-administration.

Conclusions

The present model provides a satisfactory explanation of escalated drug intake and suggests a novel negative reinforcement view of addiction based on an allostatic decrease in reward function.

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Notes

  1. This reward-facilitating effect may suffice to explain the mood-elevating or euphoric effect of cocaine which is consistent with imaging studies of brain dopamine in humans (Volkow et al. 2004). Thus, cocaine would not activate directly the reward system but would via dopamine facilitate its activation by sensory stimuli (see also Gallistel 1986). This dopamine reward-modulation hypothesis of cocaine action is consistent with the general role of dopamine in regulating functionally specialized forebrain modules (Le Moal and Simon 1991). It is also supported by data showing that stimulant drugs potentiate operant responding for unconditioned sensory stimuli, such as discrete light cues (Berlyne 1969; Gomer and Jakubczak 1974), and for classically conditioned sensory stimuli (Hill 1970; Robbins 1976; Robbins and Koob 1978; Dickinson et al. 2000). Finally, this hypothesis is more directly supported by the well-documented lowering effect of cocaine on the threshold for brain reward stimulation (Esposito et al. 1978; Kornetsky and Esposito 1981; Bauco and Wise 1997).

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Acknowledgements

Serge Ahmed was supported by grants from Université Victor-Segalen Bordeaux 2, CNRS and MILDT; George Koob was supported by National Institutes of Health grant DA04398 from the National Institute on Drug Abuse. The authors would like to thank Drs. O. Ben-Shahar, K. Frantz, P. Kenny, A. Manzardo, A. Morse, L. Parsons and Y. Shaham for critical reading of an earlier version of the manuscript, Mike Arends for his assistance with manuscript preparation, and two anonymous reviewers for their constructive comments. The authors declare no financial conflict of interest.

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Correspondence to Serge H. Ahmed.

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This is publication number 14156-NP from The Scripps Research Institute. This work was presented at the annual meeting of the Society for Neuroscience, November 2001, in San Diego, CA.

An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-011-2591-y

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Ahmed, S.H., Koob, G.F. Transition to drug addiction: a negative reinforcement model based on an allostatic decrease in reward function. Psychopharmacology 180, 473–490 (2005). https://doi.org/10.1007/s00213-005-2180-z

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