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Comparison of some behavioral effects of d- and l-methamphetamine in adult male rats

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Abstract

Rationale

Both l- and d-methamphetamine (l- and d-MA) are more potent to release norpepinephrine (NE) than dopamine, and the selectivity is greater for l-MA than d-MA. Little is known of the in vivo pharmacology of l-MA.

Objective

This study compared the effects of l-MA and d-MA in assays of nociception, behavioral disruption, and impulsivity.

Methods

Antinociceptive effects of d- and l-MA were examined in two pain assays: the warm water tail withdrawal test for acute nociception and the von Frey test in complete Freund’s adjuvant (CFA)-treated rats for chronic inflammatory pain. Food-maintained operant responding and locomotion tests were used to assess generalized behavioral disruption. The 5-choice serial reaction time test (5-CSRTT) was used to assess drug-induced effects on impulse control. A delay discounting procedure was used to determine drug-induced changes in sensitivity to reinforcer delay (impulsive choice).

Results

l-MA (3.2–10 mg/kg) produced dose-dependent antinociception in both pain assays, decreased the rate of food-maintained operant responding, and decreased locomotor activity at a higher dose (17.8 mg/kg). In contrast, d-MA (0.32–3.2 mg/kg) did not produce antinociception in either assay, produced biphasic effects on response rate, and increased locomotor activity. In the 5-CSRTT, d-MA but not l-MA produced significant increase in premature responses. In the delay discounting procedure, both drugs did not affect the delay function at doses that did not increase omissions.

Conclusions

These data suggest that d- and l-MA have different behavioral profiles. Consideration should be given to these differences in future studies when l-MA is proposed for potential therapies.

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Acknowledgements

This work was supported by the National Institute on Drug Abuse of the National Institutes of Health (Awards no. R01DA034806 and R21DA040777). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA

    Justin N. Siemian & Jun-Xu Li

  2. Department of Medical Psychology, College of Humanities and Social Sciences, Shanxi Medical University, Taiyuan, Shanxi, China

    Zhaoxia Xue

  3. Center for Drug Discovery, Research Triangle Institute, Research Triangle Park, Durham, NC, USA

    Bruce E. Blough

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  1. Justin N. Siemian
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  2. Zhaoxia Xue
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Correspondence to Jun-Xu Li.

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Siemian, J.N., Xue, Z., Blough, B.E. et al. Comparison of some behavioral effects of d- and l-methamphetamine in adult male rats. Psychopharmacology 234, 2167–2176 (2017). https://doi.org/10.1007/s00213-017-4623-8

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  • DOI: https://doi.org/10.1007/s00213-017-4623-8

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