Original Article | Published:

Chronic Exposure to Methamphetamine Disrupts Reinforcement-Based Decision Making in Rats

Neuropsychopharmacology volume 43, pages 770780 (2018) | Download Citation

Abstract

The persistent use of psychostimulant drugs, despite the detrimental outcomes associated with continued drug use, may be because of disruptions in reinforcement-learning processes that enable behavior to remain flexible and goal directed in dynamic environments. To identify the reinforcement-learning processes that are affected by chronic exposure to the psychostimulant methamphetamine (MA), the current study sought to use computational and biochemical analyses to characterize decision-making processes, assessed by probabilistic reversal learning, in rats before and after they were exposed to an escalating dose regimen of MA (or saline control). The ability of rats to use flexible and adaptive decision-making strategies following changes in stimulus–reward contingencies was significantly impaired following exposure to MA. Computational analyses of parameters that track choice and outcome behavior indicated that exposure to MA significantly impaired the ability of rats to use negative outcomes effectively. These MA-induced changes in decision making were similar to those observed in rats following administration of a dopamine D2/3 receptor antagonist. These data use computational models to provide insight into drug-induced maladaptive decision making that may ultimately identify novel targets for the treatment of psychostimulant addiction. We suggest that the disruption in utilization of negative outcomes to adaptively guide dynamic decision making is a new behavioral mechanism by which MA rigidly biases choice behavior.

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Acknowledgements

This study was supported by public health service grants DA041480 and DA043443, NARSAD, the Charles B.G. Murphy Fund, and the State of CT Department of Mental Health Services.

Author information

Author notes

    • Katherine M Rich
    •  & Nathaniel J Smith

    These two authors contributed equally to this work.

Affiliations

  1. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    • Stephanie M Groman
    • , Nathaniel J Smith
    • , Daeyeol Lee
    •  & Jane R Taylor
  2. Department of Psychology, Yale University School of Medicine, New Haven, CT, USA

    • Katherine M Rich
    • , Daeyeol Lee
    •  & Jane R Taylor
  3. Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA

    • Daeyeol Lee

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Correspondence to Stephanie M Groman.

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DOI

https://doi.org/10.1038/npp.2017.159

Supplementary Information accompanies the paper on the Neuropsychopharmacology website (http://www.nature.com/npp)