The silent and selective 5-HT(1A) antagonist, WAY 100635, produces via an indirect mechanism, a 5-HT(2A) receptor-mediated behaviour in mice during the day but not at night

Document Type

Article

Publication Title

Journal of Neural Transmission

Abstract

The head-twitch response (HTR) in rodents is considered to be a functional index for the activation of 5-HT(2A) receptors. Intraperitoneal administration of the silent and selective 5-HT(1A) receptor antagonist, WAY 100635, produced the HTR in mice in a dose-dependent bell-shaped manner. The induced behaviour followed a diurnal pattern in that WAY 100635 only produced a robust HTR frequency during the light period of the 24 h daily cycle. Pretreatment with the selective 5-HT(2A/C) receptor antagonist, SR 46349B, potently, and in a dose-dependent manner attenuated the induced behaviour. It appears that WAY 100635 produces the HTR indirectly via disinhibition of endogenous serotonergic inhibitory tone operating on the somatodenritic pulse-modulating 5-HT(1A) autoreceptors. The latter antagonism seems to potentiate endogenous 5-HT release in serotonergic terminal field synapses which subsequently stimulates postsynaptic 5-HT(2A) receptors to produce the head-twitch behaviour.

First Page

635

Last Page

643

DOI

10.1007/s007020050085

Publication Date

10-15-1998

This document is currently not available here.

Share

COinS