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Comparison of single-dose and extended methamphetamine administration on reversal learning in rats

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Abstract

Rationale

Protracted use of methamphetamine (mAMPH) can result in long-term impairments in cognitive function in humans. A previous study reported reversal-specific learning impairments in rats after a binge administration of mAMPH. Several studies show that extended exposure to mAMPH may confer protection against cognitive impairments and the insult to monoamine systems typically observed after larger binge doses.

Objectives

To explore this issue, we compared the effects of escalating and single doses of mAMPH (and saline, SAL) on retention, reversal learning, and post-mortem analysis of dopamine and serotonin transporters, DAT and SERT.

Methods

Rats learned to discriminate equiluminant stimuli and then were treated with either: (1) 4 weeks of mAMPH increasing by 0.3 mg/kg, culminating in 6 mg/kg (mAMPHescal); (2) 4 weeks of SAL with a single dose of 6 mg/kg on the last day of treatment (mAMPHsingle); or (3) 4 weeks of SAL. Following treatment, rats were tested on retention and reversal learning, with subsequent analysis of DAT and SERT binding across subregions of the striatum and frontoparietal cortex, respectively.

Results

Retention of the pretreatment discrimination was not significantly impaired in either mAMPH treatment group. A significant decrease in ventrolateral striatal DAT binding was observed only in the mAMPHsingle group and frontoparietal SERT was unaffected by either mAMPH treatment. Both treatment groups demonstrated attenuated reversal learning, particularly on measures of accuracy and effort.

Conclusions

These results show that extended and single-dose pretreatment with mAMPH similarly and selectively affect reversal learning, even in the absence of significant DAT or SERT changes.

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Acknowledgments

This work was supported by 1SC2MH087974 (Izquierdo) and 1RO1 DA012204 (Marshall). We thank the CSULA Animal Care staff for their excellent support. We are grateful to Millie Grimes, Vivian Zeng, Chelsi Darling, and Aviva Sterns for their help with behavioral testing and data collection.

Conflict 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, Danilo Rodriguez & Alicia Izquierdo

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

    Steve J. O’Dell & John F. Marshall

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  1. Alisa R. Kosheleff
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  2. Danilo Rodriguez
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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., Rodriguez, D., O’Dell, S.J. et al. Comparison of single-dose and extended methamphetamine administration on reversal learning in rats. Psychopharmacology 224, 459–467 (2012). https://doi.org/10.1007/s00213-012-2774-1

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  • DOI: https://doi.org/10.1007/s00213-012-2774-1

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