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Chronic cocaine but not chronic amphetamine use is associated with perseverative responding in humans

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Abstract

Rationale

Chronic drug use has been associated with increased impulsivity and maladaptive behaviour, but the underlying mechanisms of this impairment remain unclear. We investigated the ability to adapt behaviour according to changes in reward contingencies, using a probabilistic reversal-learning task, in chronic drug users and controls.

Materials and methods

Five groups were compared: chronic amphetamine users (n = 30); chronic cocaine users (n = 27); chronic opiate users (n = 42); former drug users of psychostimulants and opiates (n = 26); and healthy non-drug-taking control volunteers (n = 25). Participants had to make a forced choice between two alternative stimuli on each trial to acquire a stimulus–reward association on the basis of degraded feedback and subsequently to reverse their responses when the reward contingencies changed.

Results

Chronic cocaine users demonstrated little behavioural change in response to the change in reward contingencies, as reflected by perseverative responding to the previously rewarded stimulus. Perseverative responding was observed in cocaine users regardless of whether they completed the reversal stage successfully. Task performance in chronic users of amphetamines and opiates, as well as in former drug users, was not measurably impaired.

Conclusion

Our findings provide convincing evidence for response perseveration in cocaine users during probabilistic reversal-learning. Pharmacological differences between amphetamine and cocaine, in particular their respective effects on the 5-HT system, may account for the divergent task performance between the two psychostimulant user groups. The inability to reverse responses according to changes in reinforcement contingencies may underlie the maladaptive behaviour patterns observed in chronic cocaine users but not in chronic users of amphetamines or opiates.

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Acknowledgements

The authors want to thank the volunteers who took part in this study, particularly to those who aided with recruitment, and members of Narcotics Anonymous. This work was funded by a Wellcome Trust Programme Grant (no. 076274/Z/04/Z) to Professors TW Robbins, BJ Everitt, BJ Sahakian and Dr. AC Roberts and carried out within the University of Cambridge Behavioural and Clinical Neurosciences Institute (supported by a joint award from the MRC and the Wellcome Trust). Data acquisition was supported in part by Clinical Pharmacology & Discovery Medicine, GlaxoSmithKline R&D. KD Ersche holds the Betty Behrens Research Fellowship from Clare Hall College, Cambridge (U.K.) and was supported by the Fund for Addenbrooke’s and the Grindley Fund. JP Roiser held an MRC Research Studentship and is currently a recipient of the Raymond Way Fellowship at the Institute of Neurology, University College London (UK).

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Authors and Affiliations

  1. Department of Psychiatry, Brain Mapping Unit, School of Clinical Medicine, University of Cambridge, Box 255, Addenbrooke’s Hospital, Cambridge, UK

    Karen D. Ersche

  2. Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, UK

    Karen D. Ersche, Jonathan P. Roiser, Trevor W. Robbins & Barbara J. Sahakian

  3. Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Box 189, Addenbrooke’s Hospital, Cambridge, UK

    Jonathan P. Roiser & Barbara J. Sahakian

  4. Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge, UK

    Trevor W. Robbins

  5. Institute of Cognitive Neuroscience, 17 Queen Square, London, WC1N 3AR, UK

    Jonathan P. Roiser

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  1. Karen D. Ersche
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Correspondence to Karen D. Ersche.

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Ersche, K.D., Roiser, J.P., Robbins, T.W. et al. Chronic cocaine but not chronic amphetamine use is associated with perseverative responding in humans. Psychopharmacology 197, 421–431 (2008). https://doi.org/10.1007/s00213-007-1051-1

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