Original Investigation

Psychopharmacology

, Volume 182, Issue 1, pp 95-103

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

  • Sevil YasarAffiliated withDivision of Geriatric Medicine and Gerontology, Johns Hopkins University School of MedicinePreclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Department of Health and Human Services, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health
  • , Jozsef GaalAffiliated withMegaPharma Ltd
  • , Zuzana JustinovaAffiliated withPreclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Department of Health and Human Services, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health
  • , Jack BergmanAffiliated withDepartment of Psychiatry, Harvard Medical School, ADARC, McLean Hospital Email author 

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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

Amphetamine Cocaine Deprenyl Drug discrimination Methamphetamine p-Fluoro-l-deprenyl Self-administration Squirrel monkey