Interaction of serotonin autoreceptor antagonists in the rat dorsal raphe nucleus: an in vitro fast cyclic voltammetry study

5-HT1A, 5-HT18 and 5-HT1D receptors are known to function as 5-HT autoreceptors in the rat dorsal raphe nucleus (DRN), modulating local 5-HT efflux, However, there are no studies on the simultaneous blockade of these receptors in the DRN. We investigated the effect of 5-HT18 and 5-HT1D receptor antagonists on 5-HT efflux in rat DRN, alone and in the presence of 5-HT1A receptor antagonists, using the technique of fast cyclic voltammetry. The 5-HT,A receptor antagonist, WAY 100635, and the 5-HT1B receptor antagonist, SB-224289, had no effect on 5-HT efflux while the 5-HT1B/1D receptor antagonist, GR 127935, produced a small decrease in 5-HT afflux. In contrast, the 5-HT1D receptor antagonist, BRL 15572, produced a significant increase in 5-HT efflux. Go-perfusion of WAY 100635 and SB-224289 significantly increased 5-HT efflux. In addition, WAY 100635 reversed the small inhibition of 5-HT efflux observed with GR 127935 but had no effect on the BRL 15572-induced increase. Antagonism of all three 5-HT autoreceptors with SB-224289, BRL 15572 and WAY 100635 significantly increased 5-HT afflux. These data confirm that 5-HT afflux within the DRN is under the control of 5-HT1A, 5-HT1B and 5-HT1D autoreceptors and elevation of 5-HT efflux was greatest following antagonism of 5-HT,A and 5-HT1B receptors. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.