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

Department of Neuropharmacology, Glaxo Group Research Ltd, Park Road, Ware, Hertfordshire SG12 ODP, UK

Nicola Cole

Department of Neuropharmacology, Glaxo Group Research Ltd, Park Road, Ware, Hertfordshire SG12 ODP, UK

Guy Higgins

Department of Neuropharmacology, Glaxo Group Research Ltd, Park Road, Ware, Hertfordshire SG12 ODP, UK

Wasyl Feniuk

Department of Neuropharmacology, Glaxo Group Research Ltd, Park Road, Ware, Hertfordshire SG12 ODP, UK

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.

Journal of Psychopharmacology, Vol. 5, No. 3, 196-201 (1991)
DOI: 10.1177/026988119100500303


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