Effect of dotarizine on K(+)-stimulated [3H]-serotonin and [3H]-acetylcholine release from rat hippocampus

1. The effect of the diphenylmethyl-piperazine derivative dotarizine on K(+)-stimulated release of [3H]serotonin ([3H]5-HT) and [3H]acethylcholine ([3H]Ach) in rat hippocampal slices was studied. 2. Dotarizine at a concentration of 10(-6) M significantly decreased the basal [3H]5-HT release and, at a concentration of 10(-5) M, it significantly decreased the K(+)-stimulated [3H]5-HT release compared to vehicle controls. 3. Dotarizine, at a concentration of 5 x 10(-7) M, significantly increased both basal and K(+)-stimulated [3H]Ach release. At higher concentrations (10(-6) and 2 x 10(-6) M), dotarizine did not change the basal release but significantly increased the K(+)-stimulated [3H]Ach release. The effect of dotarizine on K(+)-stimulated [3H]Ach release decreased 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 could account for the facilitation of [3H]Ach release.