Further evaluation of the reinforcing effects of the novel cocaine analog 2β-propanoyl-3β-(4-tolyl)-tropane (PTT) in rhesus monkeys |
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| Authors: | Anne M Birmingham Susan H Nader Kathleen A Grant Huw M L Davies Michael A Nader |
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| Institution: | (1) Center for the Neurobiological Investigation of Drug Abuse, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA, US;(2) Department of Chemistry, SUNY Buffalo, Natural Science and Mathematics Complex, Box 603000, Buffalo, New York, USA, US;(3) Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard Winston-Salem, NC 27157-1083, USA, US |
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| Abstract: | 2β-Propanoyl-3β-(4-tolyl)-tropane (PTT) is a cocaine analog which has been shown in rhesus monkeys to have cocaine-like discriminative stimulus
effects and a long duration of action (>8 h), yet does not function as a reinforcer when substituted for cocaine in monkeys
responding under a fixed-interval 5-min schedule (Nader et al. 1997). The purpose of the present study was to evaluate the
reinforcing effects of PTT under a fixed-ratio (FR) schedule and to determine if decreasing the inter-injection interval would
influence the reinforcing effects of PTT. Male rhesus monkeys (n=3) were trained to respond under a multiple FR 30 food-drug-food schedule. When responding was stable, cocaine (0.003–0.3 mg/kg
per injection) or PTT (0.001–0.03 mg/kg per injection) was available during the drug component for at least five consecutive
sessions and until stable responding was observed. To investigate whether the inter-injection interval would influence PTT-maintained
response rates, the time-out (TO) following PTT injections was reduced from 180 or 300 s to 10 s for at least five consecutive
sessions. Cocaine-maintained response rates were characterized as an inverted-U shaped function of dose, with peak rates maintained
by 0.03 mg/kg per injection cocaine. PTT (0.001–0.03 mg/kg per injection) maintained response rates significantly higher than
rates maintained by the PTT vehicle, but significantly lower than cocaine-maintained response rates; PTT intake increased
with dose. A reduction of the TO following PTT injections to 10 s did not alter PTT-maintained response rates or total session
intake. Self-administered PTT was more potent than cocaine at decreasing food-maintained responding. These results suggest
that for long-acting compounds like PTT, reinforcing effects are more likely to be observed when the drug is available under
a ratio-based schedule, compared to an interval-based schedule.
Received: 3 May 1997 / Final version: 11 October 1997 |
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| Keywords: | Cocaine Tropanes Dopamine transporter Self-administration Rhesus monkey |
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