Alnespirone and buspirone have anxiolytic-like effects in a conflict procedure in rats by stimulating 5-HT(1A) receptors

We studied the anxiolytic-like activity of alnespirone and buspirone, two 5-HT(1A) receptor agonists, in a modified Geller-Seifter conflict model, and examined the role of 5-HT(1A) receptors by studying whether WAY-100635, a selective antagonist at these receptors, blocked their effects. Administered s.c. 30 minutes before testing, 0.5 and 1 mg/kg alnespirone significantly increased punished responding, whereas lower doses (0.125 and 0.25 mg/kg) had no effect. At 1 mg/kg, alnespirone significantly reduced the rates of unpunished responding. One dose of buspirone (1 mg/kg) significantly increased punished responding and reduced unpunished responding. Lower doses were ineffective. Administered s.c. 40 minutes before testing, WAY-100635 had no effect on any parameter but completely antagonized the effects of alnespirone (1 mg/kg) and buspirone (1 mg/kg) on punished responding. The ability of buspirone to reduce unpunished responding was not antagonized by WAY-100635, probably reflecting a sedative effect of buspirone due to dopamine D₂ receptor blockade. The results suggest that alnespirone and buspirone have anxiolytic-like activity in a conflict procedure by stimulating 5-HT(1A) receptors, presumably at a presynaptic level. Like buspirone, alnespirone may have useful effects in the treatment of anxiety disorders. (C) 2000 Lippincott Williams and Wilkins.