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Work aversion and associated changes in dopamine and serotonin transporter after methamphetamine exposure in rats

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Abstract

Rationale

Methamphetamine (mAMPH) administration in animals can lead to a variety of cognitive and behavioral deficits. We previously reported non-acute reversal learning impairments after a single-day administration of mAMPH, providing evidence of this drug’s selective effects on inhibitory control. Effortful decision-making (i.e., how much effort to invest in rewards) is an aspect of cognition that has not yet been explored after mAMPH.

Objectives

Given that frontostriatal circuitry mediating this type of choice is vulnerable to the effects of mAMPH, we tested the hypothesis that mAMPH may also affect decision-making involving effort, another form of cognitive flexibility.

Methods

We examined the non-acute effects of an experimenter-administered single day of mAMPH on effort discounting. In this task, rats previously treated with mAMPH or saline (SAL) could select a high reward at the cost of climbing over a tall barrier or a low reward with no barrier impeding its procurement.

Results

Following treatment, mAMPH rats were more work-averse than SAL rats. A control task showed there were no treatment group differences when the high and low rewards involved equal work: all rats chose the high reward preferentially. There were no significant treatment group differences in [125I]RTI-55 binding to dopamine and serotonin transporters (DAT, SERT) in any of the regions assayed; however, there were significant correlations of accumbens DAT and cingulate SERT with post-treatment performance.

Conclusions

These findings suggest that even modest dose mAMPH exposure has long-lasting effects on effortful decision-making and may do so through influences on forebrain monoaminergic systems.

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Acknowledgements

This work was supported by 1SC2MH087974 (Izquierdo) and 1RO1 DA012204 (Marshall). We thank the CSULA Animal Care staff and Dr. Andrew Holmes for comments on an earlier version of the paper.

Disclosure/conflicts of interest

There is nothing to disclose, nor are there any conflicts of interest.

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Authors and Affiliations

  1. Department of Psychology, California State University, Los Angeles, 5151 State University Drive, Los Angeles, CA, 90032, USA

    Alisa R. Kosheleff, Millie Grimes & Alicia Izquierdo

  2. Department of Neurobiology and Behavior, University of California, Irvine, CA, 92617, USA

    Steve J. O’Dell & John F. Marshall

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  1. Alisa R. Kosheleff
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  2. Millie Grimes
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  3. Steve J. O’Dell
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  4. John F. Marshall
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  5. Alicia Izquierdo
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Correspondence to Alicia Izquierdo.

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Kosheleff, A.R., Grimes, M., O’Dell, S.J. et al. Work aversion and associated changes in dopamine and serotonin transporter after methamphetamine exposure in rats. Psychopharmacology 219, 411–420 (2012). https://doi.org/10.1007/s00213-011-2367-4

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