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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.

journal_name

Psychopharmacology (Berl)

journal_title

Psychopharmacology

authors

Czoty PW,Tran P,Thomas LN,Martin TJ,Grigg A,Blough BE,Beveridge TJ

doi

10.1007/s00213-015-3875-4

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

2405-14

issue

eissn

0033-3158

issn

1432-2072

pii

10.1007/s00213-015-3875-4

journal_volume

232

pub_type

杂志文章

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