Reinforcing and discriminative stimulus effects of beta-CIT in rhesus monkeys.
beta-CIT (also designated RTI-55) is one of a series of 2 beta-carbomethoxy-3 beta-phenyltropane cocaine analogues that have recently been synthesized for characterizing the dopamine transporter and its function. The present study was designed to examine the behavioral effects of beta-CIT in rhesus monkeys. Two monkeys were allowed to self-administer cocaine (0.01 or 0.03 mg/kg/inj, IV, fixed-ratio 10, 1 h/day) in baseline sessions. When behavior was stable, beta-CIT (0.0007-0.003 mg/kg/inj, IV) was made available for self-administration for several consecutive sessions. beta-CIT maintained responding above saline levels in both monkeys. Two other monkeys were trained to discriminate cocaine (0.2 or 0.4 mg/kg, IM) from saline in a two-lever, food-reinforced drug discrimination paradigm. beta-CIT (0.012-0.025 mg/kg, IV) fully substituted for cocaine as a discriminative stimulus. In both preparations, beta-CIT was at least eightfold more potent than cocaine and had a longer duration of action. Thus, beta-CIT has cocaine-like behavioral effects indicative of a functional interaction with the dopamine transporter.
Weed
M R
MR
University of Chicago, Department of Pharmacological and Physiological Sciences, IL 60637, USA.
Mackevicius
A S
AS
Kebabian
J
J
Woolverton
W L
WL
D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008253:Macaca mulatta; D008297:Male; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology
C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine