EFFECT OF DOTARIZINE ON K-STIMULATED [H-3] SEROTONIN AND [H-3] ACETYLCHOLINE-RELEASE FROM RAT HIPPOCAMPUS()

1. The effect of the diphenylmethyl piperazine derivative dotarizine o n K+ stimulated release of [H-3]serotonin ([H-3]5-HT) and [H-3]acethyl choline ([H-3]Ach) in rat hippocampal slices was studied. 2. Dotarizin e at a concentration of 10(-6) M significantly decreased the basal [H- 3]S-HT release and, at a concentration of 10(-5) M, it significantly d ecreased the K+-stimulated [H-3]5-HT release compared to vehicle contr ols. 3. Dotarizine, at a concentration of 5 x 10(-7) M, significantly increased both basal and K+-stimu lated [H-3]Ach release. At higher co ncentrations (10(-6) and 2 x 10(-6) M), dotarizine did not change the basal release but significantly increased the K+-stimulated [H-3]Ach r elease. The effect of dotarizine on K+-stimulated [H-3]Ach release dec reased with increasing dotarizine concentrations. 4. It is speculated that, in addition to its Ca2+ antagonistic activity, dotarizine exerts an antagonistic effect on the presynaptic 5-HT autoreceptors, which c ould account for the facilitation of [H-3]Ach release. Copyright (C) 1 997 Elsevier Science Inc.