Inhibition of DOI-induced wet dog shakes in the guinea-pig by 5-HT2 receptor antagonists

Abstract

The preferential 5-HT ₂/5-HT_1C receptor agonist DOI (0.1-4 mg/kg s.c.) caused an increase in locomotor activity, grooming and 'wet-dog' shakes (WDS) in the adult guinea-pig. The DOI-induced WDS behaviour was potently inhibited by several antagonists that have high affinity for the 5-HT₂ binding site. The WDS response is likely to be centrally-mediated since the effects of peripherally administered DOI were poorly antagonized by the peripherally-acting 5-HT₂ receptor antagonist BW501C67. Although these studies do not exclude an effect of DOI at 5-HT_1C receptors, the high potency of ketanserin and spiperone in attenuating the effects of DOI would suggest an effect at the 5-HT₂ receptor. The present data suggest that antagonism of the directly-acting agonist DOI may be useful for assessing the selectivity and duration of action of centrally-acting 5-HT₂ receptor antagonists in the guinea-pig.