SEROTONIN-INDUCED PAW EDEMA IN THE RAT - PHARMACOLOGICAL PROFILE

1. Serotonin (5-HT) induced a linear increase in paw weight in rats wi thin 1 hr of an intraplantar injection (50 mu l vol) over a concentrat ion range of 0.005-0.2 mg/ml. At the 0.2 mg/ml concentration, a 16-fol d increase in paw weight was observed as compared to saline-injected c ontrols. 2. Serotonin antagonists, such as LY53857, were the most effe ctive antagonists of 5-HT induced paw swelling, producing near complet e antagonism and an approximate ED(50) of 0.1 mg/kg. A mixed 5-HT/hist amine antagonist, cyproheptadine, also produced a nearly complete inhi bition of the 5-HT response with an approximate ED(50) of 1.3 mg/kg. 3 . Dopamine agonists (pergolide, quinpirole), yohimbine, dexamethasone and nifedipine also produced a significant degree of antagonism of the 5-HT response.4. Clonidine, prazocin, chlorpheniramine, cimetidine, v arious dopamine antagonists, imipramine, cyclosporine A, piroxicam and superoxide dismutase were all ineffective at altering the paw swellin g response to 5-HT.