Effects of methamphetamine isomers on d-methamphetamine self-administration and food-maintained responding in male rats

M. T. Bardo, E. D. Denehy, L. R. Hammerslag, L. P. Dwoskin, B. E. Blough, A. Landavazo, J. Bergman, S. J. Kohut

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1 Scopus citations

Abstract

Rationale: Methamphetamine (METH) abuse is generally attributed to the d-isomer. Self-administration of l-METH has been examined only in rhesus monkeys with a history of cocaine self-administration or drug-naïve rats using high toxic doses. Objectives: In this study, the ability of l-METH and, for comparison, d-METH to engender self-administration in experimentally naïve rats, as well as to decrease d-METH self-administration and food-maintained responding, was examined. Methods: Male Sprague-Dawley rats were used in 3 separate experiments. In experiment 1, the acquisition of l- or d-METH self-administration followed by dose-response determinations was studied. In experiment 2, rats were trained to self-administer d-METH (0.05 mg/kg/infusion) and, then, various doses of l- or d-METH were given acutely prior to the session; the effect of repeated l-METH (30 mg/kg) also was examined. In experiment 3, rats were trained to respond for food reinforcement and, then, various doses of l- or d-METH were given acutely prior to the session; the effect of repeated l-METH (3 mg/kg) also was examined. Results: Reliable acquisition of l- and d-METH self-administration was obtained at unit doses of 0.5 and 0.05 mg/kg/infusion respectively. The dose-response function for l-METH self-administration was flattened and shifted rightward compared with d-METH self-administration, with peak responding for l- and d-METH occurring at unit doses of 0.17 and 0.025 respectively. l-METH also was approximately 10-fold less potent than d-METH in decreasing d-METH self-administration and 2-fold lower in decreasing food-maintained responding. Tolerance did not occur to repeated l-METH pretreatments on either measure. Conclusions: As a potential pharmacotherapeutic, l-METH has less abuse liability than d-METH and its efficacy in decreasing d-METH self-administration and food-maintained responding is sustained with repeated treatment.

Original languageEnglish
Pages (from-to)3557-3565
Number of pages9
JournalPsychopharmacology
Volume236
Issue number12
DOIs
StatePublished - Dec 1 2019

Bibliographical note

Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

  • Dose-response
  • Food reinforcement
  • Rat
  • Self-administration
  • Stimulant use disorders
  • d-Methamphetamine
  • l-Methamphetamine

ASJC Scopus subject areas

  • Pharmacology

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