Development of a translational model to screen medications for cocaine use disorder I: Choice between cocaine and food in rhesus monkeys

摘要

Background Homologous cocaine self-administration procedures in laboratory animals and humans may facilitate translational research for medications development to treat cocaine dependence. This study, therefore, sought to establish choice between cocaine and an alternative reinforcer in rhesus monkeys responding under a procedure back-translated from previous human studies and homologous to a human laboratory procedure described in a companion paper. Methods Four rhesus monkeys with chronic indwelling intravenous catheters had access to cocaine injections (0, 0.043, 0.14, or 0.43 mg/kg/injection) and food (0, 1, 3, or 10 1 g banana-flavored food pellets). During daily 5 h sessions, a single cocaine dose and a single food-reinforcer magnitude were available in 10 30-min trials. During the initial “sample” trial, the available cocaine and food reinforcer were delivered non-contingently. During each of the subsequent nine “choice” trials, responding could produce either the cocaine or food reinforcer under an independent concurrent progressive-ratio schedule. Results Preference was governed by the cocaine dose and food-reinforcer magnitude, and increasing cocaine doses produced dose-dependent increases in cocaine choice at all food-reinforcer magnitudes. Effects of the candidate medication lisdexamfetamine(0.32–3.2 mg/kg/day) were then examined on choice between 0.14 mg/kg/injection cocaine and 10 pellets. Under baseline conditions, this reinforcer pair maintained an average of approximately 6 cocaine and 3 food choices. Lisdexamfetamine dose-dependently decreased cocaine choice in all monkeys, but food choice was not significantly altered. Conclusions These results support utility of this procedure in rhesus monkeys as one component of a platform for translational research on medications development to treat cocaine use disorder.