The head-twitch response (HTR) in rodents is considered to be a functional index for the activation of 5-HT2A receptors. Intraperitoneal administration of the silent and selective 5-HT1A 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-HT2A/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-HT1A autoreceptors. The latter antagonism seems to potentiate endogenous 5-HT release in serotonergic terminal field synapses which subsequently stimulates postsynaptic 5-HT2A receptors to produce the head-twitch behaviour.
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Similar content being viewed by others Explore related subjectsDiscover the latest articles and news from researchers in related subjects, suggested using machine learning. Author information Authors and AffiliationsDepartment of Pharmacology, Kirksville College of Osteopathic Medicine, Kirksville, MO, U.S.A., , , , , , US
N. A. Darmani
Received September 22, 1997; accepted December 12, 1997
About this article Cite this articleDarmani, N. The silent and selective 5-HT1A antagonist, WAY 100635, produces via an indirect mechanism, a 5-HT2A receptor-mediated behaviour in mice during the day but not at night . J Neural Transm 105, 635–643 (1998). https://doi.org/10.1007/s007020050085
Issue Date: September 1998
DOI: https://doi.org/10.1007/s007020050085
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