Four-choice drug discrimination in pigeons.

(+)Amphetamine was added as a training stimulus for pigeons previously trained to discriminate among pentobarbital, morphine and saline using a three-choice procedure. Pigeons quickly learned the four-choice drug discrimination. Generalization from the training drugs was similar to that established with simpler drug discriminations; pentobarbital generalized to chlordiazepoxide, morphine generalized to methadone, and (+)amphetamine generalized to cocaine and methamphetamine. Low doses of phencyclidine generalized to saline, while higher doses partially generalized to pentobarbital and (+)amphetamine. When dose-response curves were redetermined with a cumulative-dosing procedure, the same pattern of generalization occurred as under single-dose procedures. Dose-response curves were quantal under both the single-dose and the cumulative-dosing procedures. The four-choice procedure offers some important advantages for studying the discriminative stimulus effects of drugs that interact with multiple receptor subtypes and for studying drug mixtures.