Discriminative stimulus properties of histamine H1-antagonists in animals trained to discriminate d-amphetamine or pentobarbital.

Pigeons were trained to discriminate i.m. administered d-amphetamine (AMPH) or pentobarbital (PB) from saline with responding maintained under a fixed-ratio 30 schedule of food delivery. Rhesus monkeys were trained to discriminate intragastrically administered AMPH or PB from saline using a signaled shock-avoidance trial procedure. In AMPH-trained pigeons the histamine H1-antagonists tripelennamine, diphenhydramine and chlorpheniramine consistently produced greater than 80% AMPH-appropriate responding. Pyrilamine substituted for AMPH in two of three pigeons. In contrast, chlorcyclizine, hydroxyzine, promethazine and the histamine H2-antagonist cimetidine all failed to produce AMPH-appropriate responding. None of the histamine H1-antagonists tested substituted for PB in PB-trained pigeons. In AMPH-trained monkeys, only tripelennamine completely substituted for AMPH. Whereas chlorpheniramine, diphenhydramine and pyrilamine did not produce AMPH-appropriate responding in monkeys, these compounds did produce observable excitation and convulsions. As with the PB-trained pigeons, none of the histamine H1-antagonists tested substituted for PB in monkeys. The results of the present study demonstrate that histamine H1-antagonists have differential discriminative stimulus properties in both pigeons and monkeys. Specifically, histamine H1-antagonists known to produce more central nervous system stimulation in humans share discriminative stimulus properties with AMPH and/or produce observable signs of stimulation in monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)