Effects of the dopamine/norepinephrine releaser phenmetrazine on cocaine self-administration and cocaine-primed reinstatement in rats
Like other monoamine releasers such as D-amphetamine, chronic treatment with phenmetrazine can attenuate cocaine self-administration in monkeys.
The present studies extended this finding to rodents and to cocaine-primed reinstatement, a putative laboratory animal model of relapse.
In experiment 1, rats self-administered food pellets or injections of 0.19 mg/kg cocaine (i.v.) under a progressive-ratio schedule. When responding was stable, subcutaneous osmotic pumps were implanted containing saline or (+)-phenmetrazine (25 or 50 mg/kg per day). In experiment 2, rats self-administered injections of 0.75 mg/kg cocaine under a fixed-ratio 1 schedule in daily 6-h sessions. When responding was stable, rats were removed from the self-administration environment for 7 days and treated continuously with saline, 5 mg/kg per day D-amphetamine or phenmetrazine (25 or 50 mg/kg per day) via osmotic pumps. Rats were then returned to the self-administration context while treatment continued, and responding was extinguished by removing response-contingent stimulus changes and cocaine injections. Once responding was extinguished, reinstatement tests were conducted using cocaine injections (10 mg/kg i.p.).
Phenmetrazine decreased self-administration of cocaine, but not food pellets, during the 14-day treatment period; effects persisted for several days after treatment was discontinued. Moreover, cocaine-induced increases in responding during the reinstatement test were attenuated by D-amphetamine and both phenmetrazine doses.
These results extend the study of the effects of phenmetrazine on cocaine self-administration to a rodent model, and provide further support for the use of monoamine releasers as agonist medications for cocaine abuse.
Czoty, P. W., Phuong Tran, Thomas, L. N., Martin, T. J., Grigg, A., Blough, B. E., & Beveridge, T. J. R. (2015). Effects of the dopamine/norepinephrine releaser phenmetrazine on cocaine self-administration and cocaine-primed reinstatement in rats. Psychopharmacology, 232(13), 2405-2414. DOI: 10.1007/s00213-015-3875-4