Effect of picrotoxin and cyproheptadine pretreatment on sodium valproate induced wet dog shake behavior in rats

Sodium valproate, a broad spectrum antiepileptic elevates the brain GABA levels by various mechanisms. Histological, electrophysiological and the biochemical studies suggest a regulatory role of GABA on dopaminergic neurons. Behavioral studies in animals provide an additional evidence for interaction between GABAergic and DAergic systems. Valproate at 200-500mg/kg induces Wet Dog Shake (WDS) behavior in rats. The WDS behavior in rats and head twitch responses in mice is evoked by 5- hydroxy-tryptophan (5-HT), the 5-HT precursor, the directly acting non-selective 5-HT receptor agonists and 5-HT releasers. In order to determine the involvement of GABAergic and 5-HTergic mechanism in the induction of WDS behavior by valproate in rats, the study was taken upto investigate the effect picrotoxin and cyproheptadine pretreatment on valproate induced WDS in rats. It was observed that subconvulsant doses of picrotoxin failed to antagonize valproate induced WDS while cyproheptadine effectively antagonized valproate induced WDS behavior in rats. Based on our study we propose that GABAergic and 5-HTergic systems are involved in production and controlling WDS behavior evoked by valproate in rats.