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Chronic methamphetamine self-administration alters cognitive flexibility in male rats

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Abstract

Rationale

Methamphetamine (meth) addiction is a chronically relapsing disorder that often produces persistent cognitive deficits. These include decreased cognitive flexibility, which may prevent meth addicts from altering their habitual drug abuse and leave them more susceptible to relapse. Multiple factors including low rates of compliance with research study participation and varied drug use patterns make the relationship between cognitive flexibility and relapse difficult to establish in clinical populations.

Objectives

Here, we combined an extended-access meth self-administration paradigm with an automated set-shifting task in rats to directly compare cognitive flexibility performance with meth-seeking behavior.

Methods

Rats were pre-trained on an automated visual discrimination task, followed by 14 days of extended access (6 h/day) of meth or sucrose self-administration. They were then tested in the set-shifting task on strategy shift and reversal and subsequently assessed for cue-induced reinstatement of meth seeking.

Results

Rats with a history of meth, but not sucrose, self-administration had selective deficits in reversal learning. Specifically, meth rats had an increase in the total number of errors and perseverative errors (corresponding to the old stimulus-reward association) following the reversal shift, which correlated with prior stable meth self-administration. However, no relationship was seen between errors during the reversal and cue-induced reinstatement.

Conclusion

The lack of association between meth-induced reversal deficits and cue-induced reinstatement to meth seeking indicates that these two domains may constitute independent pathologies of meth addiction.

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Acknowledgments

This work was supported by NIH grants RO1 DA033479, R01 DA006214, R01 MH092868, C06 RR015455, NIDA training grant 5T32DA7288-20, and a grant from the Natural Sciences and Engineering Research Council of Canada to SBF. We also thank Shannon Ghee for technical assistance.

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Authors and Affiliations

  1. Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA

    Brittney M. Cox, Zackary A. Cope, Aram Parsegian, Gary Aston-Jones & Ronald E. See

  2. Department of Psychology, University of British Columbia, Vancouver, BC, Canada

    Stan B. Floresco

  3. Brain Health Institute, Rutgers University, Piscataway, NJ, USA

    Gary Aston-Jones

  4. Department of Psychology, Westmont College, 955 La Paz Road, Santa Barbara, CA, 93108, USA

    Ronald E. See

Authors
  1. Brittney M. Cox
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  2. Zackary A. Cope
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  3. Aram Parsegian
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  4. Stan B. Floresco
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  5. Gary Aston-Jones
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  6. Ronald E. See
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Corresponding author

Correspondence to Ronald E. See.

Ethics declarations

Procedures were conducted in accordance with the “Guide for the Care and Use of Laboratory Rats” (Institute of Laboratory Animal Resources on Life Sciences, National Resources Council, 1996) and approved by the IACUC of the Medical University of South Carolina.

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Cox, B.M., Cope, Z.A., Parsegian, A. et al. Chronic methamphetamine self-administration alters cognitive flexibility in male rats. Psychopharmacology 233, 2319–2327 (2016). https://doi.org/10.1007/s00213-016-4283-0

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  • DOI: https://doi.org/10.1007/s00213-016-4283-0

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