Discriminative and reinforcing effects of brotizolam in rhesus monkeys.
The reinforcing and discriminative stimulus effects of brotizolam, a benzodiazepine-hypnotic, were evaluated in rhesus monkeys. In one experiment, separate groups of monkeys (N = 3 group) were trained to discriminate pentobarbital (10 mg/kg, IG) or d-amphetamine. (0.56-1.0 mg/kg, IG) from saline, in a discrete-trials avoidance/escape paradigm. Pentobarbital (5.6-10 mg/kg), diazepam (1.0-1.7 mg/kg), and brotizolam (0.3-1.7 mg/kg) resulted in 100% drug-lever responding in all three pentobarbital-trained monkeys. In d-amphetamine-trained monkeys brotizolam administration resulted only in saline-lever responding. In another experiment, monkeys were surgically prepared with indwelling intravenous catheters and lever pressing resulted in an injection of 0.1 mg/kg/injection sodium methohexital under a fixed-ratio 10 (FR 10) schedule. Pentobarbital (0.01-0.3 mg/kg/injection) and diazepam (0.003-0.10 mg/kg/injection) maintained responding above saline control levels when substituted for methohexital. Brotizolam (0.001-0.01 mg/kg/injection) resulted in more injections received compared to saline, but fewer injections compared to pentobarbital or diazepam. Thus, results from the present experiment suggest that brotizolam would have pentobarbital-like subjective effects. However, the abuse liability of brotizolam may be lower than that for diazepam.
Nader
M A
MA
Department of Psychiatry, Pritzker School of Medicine, University of Chicago, IL 60637.
Winger
G
G
Woods
J H
JH
Woolverton
W L
WL
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001381:Azepines / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects*; D005260:Female; D008253:Macaca mulatta; D008297:Male; D008723:Methohexital / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D012055:Reinforcement Schedule; D012646:Self Administration
D001381:Azepines; C020960:brotizolam; D008723:Methohexital; D010424:Pentobarbital; D003975:Diazepam