Effects of disulfiram on choice behavior in a rodent gambling task: association with catecholamine levels

Abstract

Rationale

Gambling disorder is a growing societal concern, as recognized by its recent classification as an addictive disorder in the DSM-5. Case reports have shown that disulfiram reduces gambling-related behavior in humans.

Objectives

The purpose of the present study was to determine whether disulfiram affects performance on a rat gambling task, a rodent version of the Iowa gambling task in humans, and whether any changes were associated with alterations in dopamine and/or norepinephrine levels.

Methods

Rats were administered disulfiram prior to testing on the rat gambling task or prior to analysis of dopamine or norepinephrine levels in brain homogenates. Rats in the behavioral task were divided into two subgroups (optimal vs suboptimal) based on their baseline levels of performance in the rat gambling task. Rats in the optimal group chose the advantageous strategy more, and rats in the suboptimal group (a parallel to problem gambling) chose the disadvantageous strategy more. Rats were not divided into optimal or suboptimal groups prior to neurochemical analysis.

Results

Disulfiram administered 2 h, but not 30 min, before the task dose-dependently improved choice behavior in the rats with an initial disadvantageous “gambling-like” strategy, while having no effect on the rats employing an advantageous strategy. The behavioral effects of disulfiram were associated with increased striatal dopamine and decreased striatal norepinephrine.

Conclusions

These findings suggest that combined actions on dopamine and norepinephrine may be a useful treatment for gambling disorders.

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Acknowledgements

We thank Doug Bernhard for his technical assistance with the HPLC system.

Funding

The current study was funded through a mid-level grant provided by the Ontario Problem Gambling Research Council to PDC and BLF and by the National Institute of Drug Abuse (DA038453 to DW) and the National Institute of Neurological Disorders and Stroke (NS088528 to EJH).

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Correspondence to Bernard Le Foll.

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This study was carried out in strict accordance with the recommendations by the Canadian Council on Animal Care. The protocol was approved by the Centre for Addiction and Mental Health Animal Care Committee.

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The authors declare that they have no conflicts of interest.

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Di Ciano, P., Manvich, D.F., Pushparaj, A. et al. Effects of disulfiram on choice behavior in a rodent gambling task: association with catecholamine levels. Psychopharmacology 235, 23–35 (2018). https://doi.org/10.1007/s00213-017-4744-0

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Keywords

  • Norepinephrine
  • Dopamine
  • Gambling
  • Antabuse