Effects of two‐week chronic treatment with phendimetrazine on choice between cocaine and food in rhesus monkeys

Abstract

The clinically available schedule III anorectic phendimetrazine is a prodrug for the monoamine releaser phenmetrazine and a candidate “agonist” medication for treatment of cocaine dependence. This study examined effects of continuous 14‐day treatment with phendimetrazine on cocaine vs. food choice in nonhuman primates. Rhesus monkeys (n=4) initially responded during daily 2‐hr sessions under a concurrent schedule of food delivery (1‐g pellets, fixed‐ratio 100 schedule) and cocaine injections (0 – 0.1 mg/kg/injection, fixed‐ratio 10 schedule). During 14‐day treatment blocks, saline or (+)‐phendimetrazine (0.32 – 1.0 mg/kg/hr) was continuously infused 23 hrs/day. During saline treatment, food was primarily chosen during availability of low cocaine doses (0, 0.0032, and 0.01 mg/kg/injection), and cocaine was primarily chosen during availability of higher cocaine doses (0.032 and 0.1 mg/kg/inj). After 14 days of 1.0 mg/kg/hr phendimetrazine, tolerance developed to initial depression of food‐maintained responding, and there was a significant rightward shift in the cocaine choice dose‐effect function such that choice of 0.032 mg/kg/injection cocaine was significantly decreased by approximately 50%. Phendimetrazine was not more efficacious than 14‐day treatment with d‐amphetamine (0.032–0.1 mg/kg/hr) to decrease cocaine vs. food choice. Funded by NIH grants R01DA026946 and R01DA012790.