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Evaluation of training dose in male Sprague-Dawley rats trained to discriminate 4-methylmethcathinone

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Abstract

Rationale

Although the synthetic cathinone 4-methylmethcathinone (4-MMC, mephedrone) has been a subject of intensive research investigation, the pharmacological mechanisms involved in its interoceptive stimulus effects have yet to be fully characterized.

Objective

The present study employed drug discrimination methods in rats to compare the interoceptive stimulus properties of two different training doses of 4-MMC to other substances with similar pharmacological actions.

Methods

Sixteen male Sprague-Dawley rats were trained to discriminate either 1.0 mg/kg (N = 8) or 3.0 mg/kg (N = 8) 4-MMC from saline. Substitution tests were conducted with drugs that increase extracellular monoamine levels (d-amphetamine, (+)-methamphetamine, 4-MMC, MDMA, MDPV, and (−)-cocaine), a serotonin releaser (+)-fenfluramine, and a serotonergic (5-HT2A) hallucinogen (+)-LSD.

Results

Stimulus control was established in fewer sessions in the subjects trained with 3.0 mg/kg compared to those trained with 1.0 mg/kg 4-MMC. Cocaine, MDMA, and d-amphetamine produced full substitution in the 1.0 mg/kg 4-MMC-trained rats at doses that did not decrease response rate. However, doses of test drugs that engendered > 80% 4-MMC-lever selection concurrently produced rate-decreasing effects in rats trained to discriminate 3.0 mg/kg 4-MMC.

Conclusions

These findings further characterize the interoceptive stimulus effects of 4-MMC and indicate that these effects vary little with training dose; however, qualitative differences in substitutability of test drugs were observed between training groups. This study expands existing knowledge regarding the psychopharmacology of 4-MMC and the potential neurochemical substrates contributing to its subjective effects.

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Acknowledgements

This research was supported by a grant from the National Institutes of Health (R15DA038295). The National Institute on Drug Abuse drug control supply program provided several of the test drugs used in this study.

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Authors and Affiliations

  1. Department of Psychology, Western Michigan University, Kalamazoo, MI, 49008, USA

    Michael D. Berquist II, Nathyn A. Thompson & Lisa E. Baker

Authors
  1. Michael D. Berquist II
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  2. Nathyn A. Thompson
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  3. Lisa E. Baker
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Corresponding author

Correspondence to Lisa E. Baker.

Ethics declarations

All procedures were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (2013) and were approved by the Institutional Animal Care and Use Committee at Western Michigan University.

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The authors declare that they have no conflict of interest.

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Berquist, M.D., Thompson, N.A. & Baker, L.E. Evaluation of training dose in male Sprague-Dawley rats trained to discriminate 4-methylmethcathinone. Psychopharmacology 234, 3271–3278 (2017). https://doi.org/10.1007/s00213-017-4716-4

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  • DOI: https://doi.org/10.1007/s00213-017-4716-4

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