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.
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Funding
This study is financially supported by NIH grants K01 DA039306 (SJK), P50 DA05312 (MTB), U01 DA13519 (LPD), U01 DA043908 (LPD), and T32 DA016176 (LPD).
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All experimental procedures were approved by the Institutional Animal Care and Use Committee at the University of Kentucky and conformed to the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
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Bardo, M.T., Denehy, E.D., Hammerslag, L.R. et al. Effects of methamphetamine isomers on d-methamphetamine self-administration and food-maintained responding in male rats. Psychopharmacology 236, 3557–3565 (2019). https://doi.org/10.1007/s00213-019-05327-8
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DOI: https://doi.org/10.1007/s00213-019-05327-8