The effects of acute and repeated clonidine administration on fixed-interval performance in rhesus monkeys

The effects of clonidine before, during and after 95 days of chronic administration of 100 micrograms/kg/day clonidine were investigated in five rhesus monkeys which had been trained to lever press under a fixed interval 5-min schedule of food presentation. The effects of clonidine (3-100 micrograms/kg) were generally to cause dose-related decreases in rates of responding and quarter-life, and increases in the line slopes of rate-dependency plots. Before chronic treatment, 200 micrograms/kg of clonidine caused somewhat less response rate suppression than 100 micrograms/kg. During chronic treatment, one monkey showed some development of tolerance to the rate-suppressant effects and another showed tolerance to the quarter-life effects, but the group as a whole did not show evidence of tolerance development to these effects of clonidine. Following cessation of chronic treatment, no overt signs of dependence were observed, however, some subjects did show disruption of schedule-controlled performance during the first week. In general, however, no consistent evidence for the development of tolerance or dependence to clonidine were observed under these dosing conditions.