Effects of monoamine releasers with varying selectivity for releasing dopamineorepinephrine versus serotonin on choice between cocaine and food in rhesus monkeys

摘要

Monoamine releasers constitute one class of candidate medications for treatment of cocaine abuse, and concurrent cocaine-versus-food choice procedures are potentially valuable as experimental tools to evaluate the efficacy and safety of candidate medications. This study assessed choice between cocaine and food by rhesus monkeys during treatment with five monoamine releasers that varied in selectivity to promote release of dopamine and norepinephrine (DA/NE) vs. serotonin (5HT) [m-fluoroamphetamine, (+)-phenmetrazine, (+)-methamphetamine, napthylisopropylamine and (±)-fenfluramine]. Rhesus monkeys (n=8) responded under a concurrent-choice schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0 – 0.1 mg/kg/inj, fixed-ratio 10 schedule). Cocaine choice dose-effect curves were determined daily during continuous seven-day treatment with saline or each test compound dose. During saline treatment, cocaine maintained a dose-dependent increase in cocaine choice, and the highest cocaine doses (0.032 – 0.1 mg/kg/inj) maintained almost exclusive cocaine choice. Efficacy of monoamine releasers to decrease cocaine choice corresponded to their pharmacological selectivity to release DA/NE vs. 5HT. None of the releasers reduced cocaine choice or promoted reallocation of responding to food choice to the same extent as substituting saline for cocaine. These results extend the range of conditions across which DA/NE-selective releasers have been shown to reduce cocaine self-administration.