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

Abstract

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.

• Authors: Paul W Czoty, Phuong Tran, Leanne N Thomas, Thomas J Martin, Amanda Grigg, Bruce E Blough, Thomas J R Beveridge
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 232 Issue 13 Pg. 2405-14 (Jul 2015) ISSN: 1432-2072 [Electronic] Germany
• PMID: 25673020 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cocaine
• Dopamine
• Norepinephrine
• Phenmetrazine

Topics

• Animals
• Cocaine (administration & dosage)
• Cocaine-Related Disorders (drug therapy, metabolism)
• Dopamine (metabolism)
• Eating (drug effects, physiology)
• Macaca mulatta
• Male
• Norepinephrine (metabolism)
• Phenmetrazine (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reinforcement, Psychology
• Self Administration