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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46334/1/213_2005_Article_BF02244198.pd

Assessment of ropinirole as a reinforcer in rhesus monkeys

Background: Ropinirole, a D-z/D-3/5-HT1A agonist, is used for the treatment of Parkinson's disease and restless leg syndrome, and is currently being evaluated as a treatment for cocaine dependence. However, there is little information available on ropinirole's reinforcing effects. Methods: The current study tested ropinirole in monkeys (n = 7) trained to self administer cocaine on a fixed-ratio 25 (FR 25) schedule of reinforcement to determine if it would function as a reinforcer. In addition, a behavioral economics approach was used in four monkeys to compare the reinforcing effectiveness of ropinirole to cocaine. Results: Cocaine (0.01-0.3 mg/kg/injection) functioned as a reinforcer in all monkeys under the FR 25 schedule, and ropinirole (0.01-0.1 mg/kg/injection) functioned as a reinforcer in all but one. Furthermore, cocaine was a more effective reinforcer than ropinirole as indexed by demand functions. Conclusion: The current data indicate that ropinirole has reinforcing effects in monkeys, although its effectiveness as a reinforcer is relatively weak. Published by Elsevier Ireland Ltd

Evaluation of the abuse liability of aminorex

Aminorex is a cyclic phenylisopropylamine that has been marketed as an anorectic. Despite obvious pharmacological similarities to the amphetamines, little is known about its liability for abuse. In the present study, one group of rhesus monkeys (n = 3) was prepared with intravenous catheters and allowed to self-administer either methohexital or saline in daily experimental sessions. When methohexital and saline self-administration were stable and clearly different, various doses of aminorex (0.001-0.1 mg/kg/injection) were made available for self-administration. Aminorex maintained self-administration above that maintained by saline and slightly lower than that maintained by methohexital in all monkeys. The discriminative stimulus effects of aminorex were evaluated in rhesus monkeys trained to discriminate d-amphetamine (n = 3) or pentobarbital (n = 4) from saline. Aminorex substituted completely for d-amphetamine as a discriminative stimulus but engendered little or no pentobarbital-appropriate responding. Aminorex stimulated locomotor activity in mice and exacerbated the withdrawal syndrome in rats that were dependent upon pentobarbital. These findings indicate that aminorex is a psychomotor stimulant that would be predicted to have significant d-amphetamine-like abuse liability in humans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31143/1/0000040.pd