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

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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.

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Acknowledgments

This research was supported by the NIDA grant P50 DA 06634.

Conflict of interest

The authors have no conflicts of interest to declare.

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Author notes

  1. Thomas J. R. Beveridge

    Present address: Ferring Pharmaceuticals, Clinical Sciences, 100 Interpace Parkway, Parsippany, NJ, 07054, USA

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA

    Paul W. Czoty, Phuong Tran, Leanne N. Thomas & Thomas J. R. Beveridge

  2. Pain Mechanisms Laboratory, Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA

    Thomas J. Martin & Amanda Grigg

  3. Center for Organic and Medicinal Chemistry, Research Triangle Institute, P.O. Box 12194, Research Triangle Park, NC, 27709, USA

    Bruce E. Blough

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  1. Paul W. Czoty
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Correspondence to Paul W. Czoty.

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Czoty, P.W., Tran, P., Thomas, L.N. et al. Effects of the dopamine/norepinephrine releaser phenmetrazine on cocaine self-administration and cocaine-primed reinstatement in rats. Psychopharmacology 232, 2405–2414 (2015). https://doi.org/10.1007/s00213-015-3875-4

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  • DOI: https://doi.org/10.1007/s00213-015-3875-4

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