Effects of the dopamine/norepinephrine releaser phenmetrazine on cocaine self-administration and cocaine-primed reinstatement in rats

• Published in: Psychopharmacology Vol. 232; no. 13; pp. 2405 - 2414
• Main Authors: Czoty, Paul W., Tran, Phuong, Thomas, Leanne N., Martin, Thomas J., Grigg, Amanda, Blough, Bruce E., Beveridge, Thomas J. R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2015; Springer; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cocaine; Cocaine - administration & dosage; Cocaine abuse; Cocaine-Related Disorders - drug therapy; Cocaine-Related Disorders - metabolism; Dopamine; Dopamine - secretion; Drug therapy; Eating - drug effects; Eating - physiology; Macaca mulatta; Male; Neurosciences; Norepinephrine; Norepinephrine - secretion; Original Investigation; Pharmacology/Toxicology; Phenmetrazine - pharmacology; Physiological aspects; Psychiatry; Rats; Rats, Sprague-Dawley; Reinforcement (Psychology); Self Administration; Studies; Therapy; United States; Reinforcement; Monoamine; Relapse; Rat; Reinstatement; Agonist therapy
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-015-3875-4

Rationale Like other monoamine releasers such as D-amphetamine, chronic treatment with phenmetrazine can attenuate cocaine self-administration in monkeys. Objectives The present studies extended this finding to rodents and to cocaine-primed reinstatement, a putative laboratory animal model of relapse. Methods 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.). Results 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. Conclusions 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.