Evaluation of the discriminative stimulus and reinforcing effects of sertraline in rhesus monkeys.
Rhesus monkeys (N = 4) were allowed to self-administer cocaine (0.03 mg/kg/injection) under a fixed-ratio 10 (FR 10) schedule during daily 2-h experimental sessions. When responding was stable, a variety of doses of sertraline, a serotonin reuptake blocker under development as an antidepressant, were made available for self-administration. Baseline conditions were reinstated between doses of sertraline. Cocaine 0.03 mg/kg/injection maintained high rates of injection, while total saline injections decreased to low levels within four to seven sessions. Sertraline (0.05-0.4 mg/kg/injection) did not maintain self-administration above saline levels in three of the four monkeys. In the fourth, responding was marginally above saline levels at two doses but was not systematically related to dose. In a second experiment, rhesus monkeys (N = 6) were trained to discriminate either d-amphetamine (0.56-1.0 mg/kg, IG) or pentobarbital (10 mg/kg, IG) from saline in a discrete-trials shock avoidance/escape paradigm. Sertraline (4.0-32 mg/kg) failed to substitute for either d-amphetamine or pentobarbital as a discriminative stimulus. These results suggest that sertraline is unlikely to have abuse potential in humans and is unlikely to have either d-amphetamine-like or pentobarbital-like subjective effects.
Vanover
K E
KE
Drug Abuse Research Center, University of Chicago, IL 60637.
Nader
M A
MA
Woolverton
W L
WL
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000661:Amphetamine; D000818:Animals; D003042:Cocaine; D005260:Female; D008253:Macaca mulatta; D008297:Male; D010424:Pentobarbital; D012054:Reinforcement, Psychology; D012646:Self Administration; D012702:Serotonin Antagonists / Q000494:pharmacology; D020280:Sertraline; D019966:Substance-Related Disorders
D012702:Serotonin Antagonists; D015057:1-Naphthylamine; D000661:Amphetamine; D010424:Pentobarbital; D003042:Cocaine; D020280:Sertraline