Discriminative stimulus effects of the novel anxiolytic buspirone

Separate groups of Long-Evans rats were trained to discriminate either 0.56 or 1.0 mg/kg buspirone i.p. in a two-lever, drug vs no-drug discrimination procedure. Training took twice as long for the lower versus the higher training-dose group. Generalization tests were conducted with buspirone (0.1–1.8mg/kg, i.p.; 0.32–10mg/kg, p.o.), pentylenetetrazole (1–18 mg/kg, i.p.), meprobamate (3.2–180 mg/kg, p.o.), haloperidol (0.01–0.32 mg/kg, i.p.), and 8-OH-DPAT (0.01–0.32 mg/kg, i.p.). Buspirone p.o. was 0.5–1.0 log10 units less potent than buspirone i.p. in producing dose-dependent generalization (i.e.> 80% buspirone-lever responding). Dose-effect functions for the 1.0 training-dose group were to the right of those for the 0.56 group. Partial generalization to meprobamate occurred in both groups, representing the first report of overlap of the buspirone discriminative stimulus with that of another anxiolytic. Complete generalization to 8-OH-DPAT occurred, consistent with buspironeʼs prominent 5HT1A-receptor activity and replicating findings in the pigeon. Partial generalization to haloperidol was concludedevery rat generalized to haloperidol, but the gradients did not increase monotonically and drug-lever responding at a given dose was inconsistent within and across rats. The haloperidol results suggest a stronger influence of the dopaminergic component in the buspirone discriminative stimulus in rats than was found with pigeons. Although a previous study found generalization to buspirone from pentylenetetrazole in baboons, there was no generalization to pentylenetetrazole from buspirone in the present study.