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OtherBEHAVIORAL PHARMACOLOGY

The Reinforcing and Discriminative Stimulus Effects of the Novel Cocaine Analog 2β-Propanoyl-3β-(4-Tolyl)-Tropane in Rhesus Monkeys

Michael A. Nader, Kathleen A. Grant, Huw M. L. Davies, Robert H. Mach and Steven R. Childers
Journal of Pharmacology and Experimental Therapeutics February 1997, 280 (2) 541-550;
Michael A. Nader
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Kathleen A. Grant
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Huw M. L. Davies
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Robert H. Mach
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Abstract

2β-propanoyl-3β-(4-tolyl)-tropane (PTT), is a cocaine analog that inhibits dopamine uptake, binding with high affinity and selectivity to the dopamine transporter. In the present study, the behavioral effects of PTT were evaluated in two models of cocaine abuse: drug self-administration and drug discrimination. In the first experiment, rhesus monkeys (n = 3) were trained to self-administer cocaine (0.03 and 0.1 mg/kg/injection, i.v.) under a fixed-interval 5-min schedule. Presession administration of PTT (0.03–0.3 mg/kg, i.v.) or cocaine (0.3–3.0 mg/kg, i.v.) were evaluated. At both self-administered doses of cocaine, PTT decreased response rates and total session intakes and was approximately 0.5 to 1.0 log units more potent than cocaine. In experiment 2, the reinforcing effects of PTT (0.003–0.1 mg/kg/injection) were evaluated in a separate group of monkeys (n = 4) responding under a fixed-interval 5-min schedule of cocaine (0.03 mg/kg/injection) presentation. When substituted for cocaine, PTT maintained response rates similar to saline-maintained rates and significantly lower than rates maintained by cocaine (0.003–0.3 mg/kg/injection). Total session PTT intake was significantly lower than cocaine intake. In experiment 3, the discriminative stimulus effects of PTT (0.003–0.1 mg/kg, i.m.) were evaluated in monkeys (n = 3) trained to discriminate cocaine (0.2 mg/kg, i.m.) from saline (0.5 ml). PTT substituted for cocaine in a dose-dependent manner and was 0.5 to 1.0 log units more potent than cocaine. At the highest PTT dose, cocaine-appropriate responding was observed 8 to 24 hr after the injection. These results demonstrated that the long-acting indirect dopamine agonist PTT was effective in decreasing cocaine self-administration and in abuse liability testing showed a unique behavioral profile, not functioning as a reinforcer when substituted for cocaine and producing discriminative stimulus effects similar to cocaine.

Footnotes

  • Send reprint requests to: Dr. Michael A. Nader, Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083.

  • ↵1 This research was supported by National Institute on Drug Abuse research grants P50 DA-06634 and DA-09142.

  • ↵2 Current address: Department of Chemistry, SUNY Buffalo, Natural Science and Mathematics Complex, Box 603000, Buffalo, NY 14260-3000.

  • Abbreviations:
    β-CIT
    2β-carbomethoxy-3β-phenyltropane
    DA
    dopamine
    FI
    fixed-interval
    FR
    fixed-ratio
    PTT
    2β-propanoyl-3β-(4-tolyl)-tropane
    NE
    norepinephrine
    QL
    quarter-life
    5-HT
    serotonin
    TO
    timeout
    • Received March 4, 1996.
    • Accepted October 7, 1996.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 280, Issue 2
1 Feb 1997
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OtherBEHAVIORAL PHARMACOLOGY

The Reinforcing and Discriminative Stimulus Effects of the Novel Cocaine Analog 2β-Propanoyl-3β-(4-Tolyl)-Tropane in Rhesus Monkeys

Michael A. Nader, Kathleen A. Grant, Huw M. L. Davies, Robert H. Mach and Steven R. Childers
Journal of Pharmacology and Experimental Therapeutics February 1, 1997, 280 (2) 541-550;

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OtherBEHAVIORAL PHARMACOLOGY

The Reinforcing and Discriminative Stimulus Effects of the Novel Cocaine Analog 2β-Propanoyl-3β-(4-Tolyl)-Tropane in Rhesus Monkeys

Michael A. Nader, Kathleen A. Grant, Huw M. L. Davies, Robert H. Mach and Steven R. Childers
Journal of Pharmacology and Experimental Therapeutics February 1, 1997, 280 (2) 541-550;
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