Effects of clonidine on operant behavior and electric shock titration in the squirrel monkey: effects of alpha 2-adrenoreceptor antagonism.

Squirrel monkeys were studied under fixed-interval schedules in which responding was maintained either by food presentation or by termination of stimuli correlated with electric shock delivery, or under a schedule in which responses decreased the intensity of electric shock, which periodically increased in intensity (shock titration). Clonidine-HCl (0.01-1.7 mg/kg) decreased responding under the fixed-interval schedules and increased the intensity at which shock was maintained under the titration schedule. Pretreatment with the alpha 2-adrenoreceptor antagonist yohimbine-HCl (0.1-1.0 mg/kg) resulted in a 3-10-fold shift to the right in the clonidine dose-response curve. Similar antagonism was seen after pretreatment with small doses of the less selective alpha-adrenoreceptor antagonist, tolazoline-HCl (3.0, 5.6 mg/kg), but not with the alpha 1 antagonist prazosin (0.1, 0.3 mg/kg). The effects of clonidine on behavior under these conditions were apparently due to actions at alpha 2-adrenoreceptor sites.