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

Autor: Bardo MT; Department of Psychology, University of Kentucky, Lexington, KY, 40536, USA. mbardo@uky.edu., Denehy ED; Department of Psychology, University of Kentucky, Lexington, KY, 40536, USA., Hammerslag LR; Department of Psychology, University of Kentucky, Lexington, KY, 40536, USA., Dwoskin LP; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536, USA., Blough BE; Research Triangle Institute, Center for Drug Discovery, Research Triangle Park, NC, USA., Landavazo A; Research Triangle Institute, Center for Drug Discovery, Research Triangle Park, NC, USA., Bergman J; McLean Hospital - Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA., Kohut SJ; McLean Hospital - Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2019 Dec; Vol. 236 (12), pp. 3557-3565. Date of Electronic Publication: 2019 Jul 26.
DOI: 10.1007/s00213-019-05327-8
Abstrakt: 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.
Databáze: MEDLINE
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