Discriminative stimulus properties of buspirone in the pigeon

The novel anxiolytic buspirone was administered to pigeons in a two-key drug discrimination task in an effort to characterize the stimulus properties of the drug and thereby aid in isolating the pharmacologic basis for its anticonflict effect. Key pecking was maintained by a schedule of reinforcement in which every 30th injection-appropriate response was reinforced by the presentation of food. Subjects were first trained to discriminate buspirone (1.0 mg/kg) from saline, and then generalization tests were conducted using a cumulative dosing procedure. Cumulative doses of buspirone (1.0-3.0 mg/kg), the buspirone analog MJ 13805 (1.0 mg/kg) and the 5-hydroxytryptamine-1A ligand 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.3-1.0 mg/kg) produced in excess of 90% buspirone-appropriate responding, whereas midazolam (0.03-1.0 mg/kg), haloperidol (0.03-1.7 mg/kg), apomorphine (0.03-1.0 mg/kg), clozapine (0.1-3.0 mg/kg), methysergide (0.1-3.0 mg/kg) and the 5-hydroxytryptamine-1B ligand 1-[3-chlorophenyl]piperazine (0.3-10.0 mg/kg) produced little or no buspirone-appropriate responding up to those doses that markedly decreased response rate. These findings support recent behavioral and receptor binding studies suggesting that serotonin receptors, and 5-hydroxytryptamine-1A receptors in particular, may be responsible for mediating the anticonflict effects of buspirone and other atypical anxiolytics. The results also corroborate other behavioral work showing that the anxiolytic effects of buspirone are most likely not mediated by the dopaminergic system.