Further evaluation of the reinforcing effects of the novel cocaine analog 2beta-propanoyl-3beta-(4-tolyl)-tropane (PTT) in rhesus monkeys.
2Beta-propanoyl-3beta-(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 a 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.
Birmingham
A M
AM
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.
Nader
S H
SH
Grant
K A
KA
Davies
H M
HM
Nader
M A
MA
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D012646:Self Administration
C087634:2-propanoyl-3-(4-tolyl)tropane; D003042:Cocaine