The discriminative stimulus effects of histamine H(1)-antagonists in pigeons

Two groups of pigeons were trained to discriminate a histamine H(1)-antagonist (chlorpheniramine or promethazine) from saline with responding maintained under a fixed-ratio 30 schedule of food delivery. There was no cross-substitution with these two histamine H(1)-antagonists: that is, promethazine failed to substitute reliably for chlorpheniramine in chlorpheniramine-trained pigeons, and chlorpheniramine failed to substitute reliably for promethazine in promethazine-trained pigeons. Among the other histamine H(1)-antagonists tested, tripelennamine consistently produced greater than 80% responding in chlorpheniramine-trained pigeons but not in promethazine-trained pigeons. In contrast, diphenhydramine consistently produced greater than 80% responding in promethazine-trained pigeons but not in chlorpheniramine-trained pigeons. Similarly, chlorcyclizine partially substituted for promethazine and failed to substitute for chlorpheniramine. d-Amphetamine substituted for chlorpheniramine in 2 of 4 pigeons and partially in a third pigeon, whereas d-amphetamine substituted for promethazine in only 1 of 4 pigeons. Pentobarbital failed to produce greater than 80% responding in either chlorpheniramine- or promethazine-trained pigeons. The results of the present study demonstrate that the histamine H(1)-antagonists, chlorpheniramine and promethazine, have differential discriminative stimulus effects in pigeons. These findings suggest that the discriminative stimulus effects of this class of compounds are not based entirely on their ability to act as antagonists at histamine H(1)-receptors.