High rates of midazolam self-administration in squirrel monkeys

Although benzodiazepines are frequently abused by humans, they usually maintain lower rates of self-administration behavior in laboratory animals than other drugs of abuse such as psychomotor stimulants or barbiturates. In the present study, intravenous (i.v.) self-administration of the short-acting benzodiazepine midazolam was evaluated in squirrel monkeys. Monkeys (n = 3) initially self-administered the short-acting barbiturate methohexital (100 microg/kg/injection) during daily 1-hour sessions under a fixed-ratio 10, 60 s time-out, schedule of i.v. drug injection. This dose of methohexital maintained high rates of responding averaging 0.9 responses per second. Midazolam was then substituted for methohexital, and midazolam dose was subsequently varied from 0.3 to 3 microg/kg/injection. Each dose of midazolam was tested for five consecutive sessions and each unit dose condition was separated by five sessions of vehicle extinction. The midazolam dose-response function was an inverted U-shaped curve, with maximal rates of self-administration responding averaging 1.01 responses/second at a dose of 1 microg/kg/injection (an average of 48 injections per 1-hour session). The rates and fixed-ratio patterns of responding maintained by self-administration of midazolam in the present study were comparable to the rates and patterns of responding maintained in squirrel monkeys by self-administration of other drugs of abuse, including cocaine, amphetamine, nicotine and tetrahydrocannabinol, under similar experimental conditions.