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Neurobiological evidence for hedonic allostasis associated with escalating cocaine use

Nature Neuroscience volume 5, pages 625–626 (2002)Cite this article

Abstract

A paradoxical aspect of the transition to drug addiction is that drug users spend progressively more time and effort to obtain drug hedonic effects that continually decrease with repeated experience1,2. According to the hedonic allostasis hypothesis3, increased craving for and tolerance to the hedonic effects of drugs result from the same chronic alteration in the regulation of brain reward function (allostasis). Here we show in rats that repeated withdrawals from prolonged cocaine self-administration produces a persistent decrease in brain reward function that is highly correlated with escalation of cocaine intake and that reduces the hedonic impact of cocaine.

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Figure 1: Relationship between elevation in ICSS reward thresholds and cocaine intake escalation.
Figure 2: Acute effect of cocaine on ICSS reward thresholds.
Figure 3: Persistent elevation in ICSS reward thresholds after cessation of prolonged access to cocaine self-administration.

Notes

  1. NOTE: A mistake was introduced during the preparation of this paper. In the AOP version, panel labels b and c in Fig. 1 were mistakenly switched. The lower left panel should be labeled b, and the upper right panel should be labeled c. This mistake has been corrected in the HTML version and will appear correctly in print. The PDF version available online has been appended.

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Acknowledgements

Supported by the Centre National de la Recherche Scientifique (S.H.A.), the Peter McManus Charitable Trust (P.J.K.) and grants from the National Institute on Drug Abuse (DA04398 to G.F.K. and DA11946 to A.M.). This is manuscript number 14258-NP from The Scripps Research Institute.

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Author notes

  1. Serge H. Ahmed and Paul J. Kenny: The first two authors contributed equally to this work.

Authors and Affiliations

  1. Laboratoire de Neuropsychobiologie des Désadaptations, Université de Bordeaux 2, CNRS-UMR 5541, 146 rue Léo-Saignat, Bordeaux, 33076, France

    Serge H. Ahmed

  2. Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA

    Serge H. Ahmed, Paul J. Kenny, George F. Koob & Athina Markou

Authors
  1. Serge H. Ahmed
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  2. Paul J. Kenny
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  3. George F. Koob
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  4. Athina Markou
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Correspondence to Serge H. Ahmed.

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The authors declare no competing financial interests.

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Ahmed, S., Kenny, P., Koob, G. et al. Neurobiological evidence for hedonic allostasis associated with escalating cocaine use. Nat Neurosci 5, 625–626 (2002). https://doi.org/10.1038/nn872

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