Alnespirone and buspirone have anxiolytic‐like effects in a conflict procedure in rats by stimulating 5‐HT1A receptors

We studied the anxiolytic‐like activity of alnespirone and buspirone, two 5‐HT1A receptor agonists, in a modified Geller–Seifter conflict model, and examined the role of 5‐HT1A 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‐HT1A receptors, presumably at a presynaptic level. Like buspirone, alnespirone may have useful effects in the treatment of anxiety disorders.