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

Bruce E. Blough; Antonio Landavazo; Michael T Bardo; Emily D Denehy; L R Hammerslag; Linda P Dwoskin; Bruce E. Blough; Antonio Landavazo; Jack Bergman; Stephen J. Kohut

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

Bardo, M. T., Denehy, E. D., Hammerslag, L. R., Dwoskin, L. P., Blough, B. E., Landavazo, A., Bergman, J., & Kohut, S. J. (2019). Effects of methamphetamine isomers on d-methamphetamine self-administration and food-maintained responding in male rats. Psychopharmacology, 236(12), 3557-3565. Advance online publication. https://doi.org/10.1007/s00213-019-05327-8

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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.