Psychopharmacology

, Volume 182, Issue 1, pp 95–103

Discriminative stimulus and reinforcing effects of p-fluoro-l-deprenyl in monkeys

Authors

  • Sevil Yasar
    • Division of Geriatric Medicine and GerontologyJohns Hopkins University School of Medicine
    • Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Department of Health and Human Services, Intramural Research ProgramNational Institute on Drug Abuse, National Institutes of Health
  • Jozsef Gaal
    • MegaPharma Ltd
  • Zuzana Justinova
    • Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Department of Health and Human Services, Intramural Research ProgramNational Institute on Drug Abuse, National Institutes of Health
    • Department of Psychiatry, Harvard Medical School, ADARCMcLean Hospital
Original Investigation

DOI: 10.1007/s00213-005-0063-y

Cite this article as:
Yasar, S., Gaal, J., Justinova, Z. et al. Psychopharmacology (2005) 182: 95. doi:10.1007/s00213-005-0063-y

Abstract

Rationale

para-Fluoro-l-deprenyl (Fludepryl), a halogenated derivative of l-deprenyl, shares structural similarities with amphetamine and may have potential as a medication for psychostimulant abuse.

Objectives

p-Fluoro-l-deprenyl was evaluated for psychomotor stimulant, discriminative stimulus, and reinforcing effects in squirrel monkeys.

Methods

One group of monkeys was trained under a ten-response fixed-ratio (FR10) schedule of stimulus termination to discriminate between methamphetamine (0.32 mg/kg, i.m.) and saline. Other monkeys were trained to self-administer i.v. cocaine under either a simple FR10 schedule or a second-order fixed-interval 5-min schedule with FR10 components.

Results

Full generalization to the methamphetamine-training stimulus was produced by an i.m. dose of 10.0 mg/kg p-fluoro-l-deprenyl. l-Deprenyl and the metabolites of p-fluoro-l-deprenyl, p-fluoro-l-amphetamine, and p-fluoro-l-methylamphetamine were more potent, producing full generalization at doses of 1.0–3.2 mg/kg. Under the FR10 schedule of drug injection, persistent self-administration behavior was maintained by i.v. cocaine injections but not by injections of vehicle or injection doses of p-fluoro-l-deprenyl up to 1.0 mg/kg. However, p-fluoro-l-deprenyl did maintain moderate levels of i.v. self-administration responding under the second-order schedule of drug injection. Peak response rates maintained by 0.1-mg/kg injections of p-fluoro-l-deprenyl were significantly greater than those associated with saline substitution, yet significantly lower than those maintained by cocaine or d-amphetamine.

Conclusions

p-Fluoro-l-deprenyl has methamphetamine-like discriminative-stimulus properties in squirrel monkeys that appear at higher doses than for its parent compound, l-deprenyl. It also appears to function as a relatively limited reinforcer of intravenous self-administration behavior in monkeys trained to self-administer i.v. cocaine.

Keywords

AmphetamineCocaineDeprenylDrug discriminationMethamphetaminep-Fluoro-l-deprenylSelf-administrationSquirrel monkey

Copyright information

© Springer-Verlag 2005