Effects of serotonin agonists on operant behavior in the squirrel monkey: quipazine, MK-212, trifluoromethylphenylpiperazine, and chlorophenylpiperazine.

The behavior of squirrel monkeys was studied under fixed-interval (FI) schedules with responding maintained either by food presentation or by termination of stimuli correlated with impending electric shock delivery (stimulus-shock termination). The 5-HT agonists m-trifluoromethylphenylpiperazine (TFMPP), m-chlorophenylpiperazine (mCPP), and 6-chloro-2(l-piperazinyl)pyrazine (MK-212) decreased responding under both the food and shock schedules (0.3-5.6 mg/kg). These decreases in responding were blocked by the nonselective 5-HT antagonists methysergide and mianserin (0.3, 1.0 mg/kg), but not by the selective 5-HT2 antagonists ketanserin (0.3-1.7 mg/kg) or pirenperone (0.001-0.1 mg/kg). Quipazine (0.3-5.6 mg/kg) decreased responding under the food schedule, and this effect was blocked by both the nonselective and selective 5-HT2 antagonists. This pattern of antagonism suggests that the decreases in responding produced by quipazine involve significant actions at 5-HT2 sites, whereas those produced by TFMPP, mCPP, and MK-212 do not. In contrast to the decreases in responding seen with the food schedules, quipazine produced moderate increases in responding under the shock schedules. Moreover, these increases in responding were not blocked by methysergide or mianserin, but instead were enhanced. The results with antagonists suggest that certain behavioral effects of quipazine are probably due to actions at 5-HT2 sites, whereas similar effects of TFMPP, mCPP, and MK-212 are more related to actions at other 5-HT receptor subtypes.