Cocaine-base smoking in rhesus monkeys: reinforcing and physiological effects.

Four rhesus monkeys were trained to smoke cocaine-base under a progressive ratio (PR) schedule, with ten smoking trials available each day. Unit dose was varied from 0.25 to 3 mg/kg, and lidocaine (2 mg/kg) was substituted for cocaine. Number of responses and break-point on the PR schedule increased with dose while the number of smoke deliveries increased only slightly. Maximum daily smoke deliveries ranged from six to nine across monkeys. When lidocaine (2 mg/kg) was substituted for cocaine-base, responding decreased to approximately half of that maintained by cocaine, and when cocaine was reinstated, higher response rates returned. Cardiovascular changes associated with cocaine smoking were monitored with an indwelling radio transmitter. There was an initial decrease in heart rate (30 s) followed by a rapid rise and decline by the end of the 15-min trials. Blood pressure increased rapidly after trial onset and returned to pretrial baseline by 15 min. Over the eight trials completed during a session, heart rate and blood pressure steadily increased over presession base-lines during the first four trials, but there was then a decline suggesting acute tolerance development. Observations of the monkeys after each trial revealed dilated pupils and slightly agitated, hyperactive behavior. These findings indicated that smoked cocaine-base was rapidly established as a reinforcer for monkeys, and the physiological effects were similar to those reported in studies of human subjects.