Histamine as a punisher in squirrel monkeys: effects of pentobarbital, chlordiazepoxide and H1- and H2-receptor antagonists on behavior and cardiovascular responses.

Squirrel monkeys pressed a key under a two-component, 30-response fixed-ratio schedule of food presentation. In both nonpunishment and punishment components, every 30th key-pressing response resulted in food presentation. In the punishment component, the 11th and 22nd response in each 30-response fixed-ratio also produced a 200msec i.v. injection of 30 to 100 microgram/kg of histamine; this resulted in about an 80% suppression of responding in the punishment component. A second group of squirrel monkeys, with arterial catheters for monitoring of blood pressure and heart rate, received automatic i.v. injections of 30 and 100 microgram/kg of histamine; key presses had no programmed consequences. Mean arterial blood pressure decreased by 5 to 20 min Hg and heart rate increased by 60 to 120 beats/min after each injection of histamine. As an effective punisher, histamine was functionally similar to other noxious stimuli such as electric shock. Behavior suppressed by histamine could be markedly increased by presession i.m. treatment with pentobarbital (3-5.6 mg/kg) or chlordiazepoxide (10-30 mg/kg). Presession i.m. treatment with 1 to 3 mg/kg of the H1-receptor antagonist, diphenhydramine, reversed the punishment effects of histamine but only enhanced the cardiovascular effects of histamine. In contrast, 10 to 30 mg/kg of the H2-receptor antagonist, cimetidine, failed to reverse the punishment effects of histamine but markedly attenuated the cardiovascular effects of histamine. Thus, histamine's suppression of responding appeared to be an H1 effect and did not appear to be related to its effects on blood pressure and heart rate.