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Research ArticleNEUROPHARMACOLOGY

Comparative Behavioral Pharmacology of Cocaine and the Selective Dopamine Uptake Inhibitor RTI-113 in the Squirrel Monkey

Leonard L. Howell, Paul W. Czoty, Michael J. Kuhar and F. Ivy Carrol
Journal of Pharmacology and Experimental Therapeutics February 2000, 292 (2) 521-529;
Leonard L. Howell
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Paul W. Czoty
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Michael J. Kuhar
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F. Ivy Carrol
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Abstract

The behavioral effects of 3β-(4-chlorophenyl)tropane-2β-carboxylic acid phenyl ester hydrochloride (RTI-113; 0.03–1.0 mg/kg), a selective dopamine uptake inhibitor, were compared with those of cocaine (0.03–3.0 mg/kg) and 1-{2-[bis(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12909; 0.03–3.0 mg/kg) in squirrel monkeys. Intermediate doses of each drug produced significant increases in response rate maintained by a fixed-interval (FI) 300-s schedule of stimulus termination, but RTI-113 was less effective than cocaine or GBR 12909. The order of potency for increasing response rate was RTI-113 ≥ cocaine > GBR 12909. In drug time course determinations, RTI-113 and GBR 12909 had longer durations of action than cocaine. RTI-113 substituted completely for cocaine in subjects trained to discriminate cocaine and saline under a two-lever drug-discrimination procedure maintained by food delivery. RTI-113 also reliably maintained self-administration behavior in subjects trained under a second-order FI 900-s schedule of i.v. cocaine delivery. Pretreatment with RTI-113 significantly decreased responding for cocaine at the highest pretreatment dose, but RTI-113 had similar effects on responding maintained by a second-order FI 900-s schedule of stimulus termination. The results indicate that the behavioral pharmacology of RTI-113 is similar to that of cocaine, further implicating a prominent role for dopamine uptake inhibition in the behavioral effects of cocaine. Its longer duration of action in conjunction with less pronounced behavioral-stimulant effects are desirable properties for a substitute pharmacotherapy for cocaine abuse. RTI-113 effectively decreased cocaine self-administration behavior, although its direct rate-altering effects may have contributed to the interactions obtained.

Footnotes

  • Send reprint requests to: Dr. Leonard L. Howell, Yerkes Regional Primate Research Center, Emory University, Atlanta, GA 30322. E-mail: leonard{at}rmy.emory.edu

  • ↵1 This research was supported in part by U.S. Public Health Service Grants DA-01161, DA-05346, DA-10344, and RR-00165 (Division of Research Resources, National Institutes of Health) and Contract Grant OND-6069 (Office of National Drug Control Policy). The Yerkes Regional Primate Research Center is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International).

  • Abbreviations:
    GBR 12909
    1-{2-[bis(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl)piperazine dihydrochloride
    FI
    fixed interval
    FR
    fixed ratio
    RTI-113
    3β-(4-chlorophenyl)tropane-2β-carboxylic acid phenyl ester hydrochloride
    • Received March 23, 1999.
    • Accepted October 13, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 292 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 292, Issue 2
1 Feb 2000
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Research ArticleNEUROPHARMACOLOGY

Comparative Behavioral Pharmacology of Cocaine and the Selective Dopamine Uptake Inhibitor RTI-113 in the Squirrel Monkey

Leonard L. Howell, Paul W. Czoty, Michael J. Kuhar and F. Ivy Carrol
Journal of Pharmacology and Experimental Therapeutics February 1, 2000, 292 (2) 521-529;

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Research ArticleNEUROPHARMACOLOGY

Comparative Behavioral Pharmacology of Cocaine and the Selective Dopamine Uptake Inhibitor RTI-113 in the Squirrel Monkey

Leonard L. Howell, Paul W. Czoty, Michael J. Kuhar and F. Ivy Carrol
Journal of Pharmacology and Experimental Therapeutics February 1, 2000, 292 (2) 521-529;
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