Effects of serotonin receptor antagonists on punished responding maintained by stimulus-shock termination or food presentation in squirrel monkeys.

The behavioral effects of a series of serotonin (5-HT) receptor antagonists were examined on punished performances maintained by termination of a stimulus correlated with shock (stimulus-shock termination) or by food presentation in squirrel monkeys. Intramuscular administration of metergoline (0.03-0.3 mg/kg), methysergide (0.1-1.0 mg/kg), cyproheptadine (0.1-1.0 mg/kg), mianserin (0.1-10 mg/kg) and cinanserin (1.0-3.0 mg/kg) increased punished responding under the stimulus-shock termination and food schedules. The 5-HT2-selective receptor antagonist pirenperone (0.001-0.3 mg/kg) and the 5-HT2 receptor ligand spiperone (0.001-0.1 mg/kg) did not increase punished responding maintained by either event. In contrast, the prototype 5-HT2 ligand ketanserin increased punished responding maintained by food at doses (i.e., 0.1-3.0 mg/kg) that only decreased behavior maintained by stimulus-shock termination. Highly significant correlations were found between the peak rate-increasing effects of the 5-HT antagonists on punished responding maintained by stimulus-shock termination and their reported affinities at 5-HT1 (r = 0.99) and 5-HT2 (r = 0.95) binding sites. In contrast, under the food schedule a significant correlation was found only between the peak rate-increasing effects of the 5-HT antagonists and their reported affinities for the 5-HT1 site (r = 0.87). These findings confirm the involvement of serotonergic pathways in punishment-suppressed operant behavior and suggest that different populations of 5-HT receptors modulate punished behavior maintained by different types of consequent events (i.e., stimulus-shock termination or food).