Effect of P-Chlorophenylalanine Pretreatment on Sodium Valproate and Dexfenfluramine Induced Wet Dog Shake Behavior in Rats

INTRODUCTION: Sodium valproate, a broad spectrum antiepileptic drug elevates the brain gamma amino butyric acid (GABA) levels by various mechanisms. Behavioral studies in animals have provided additional evidence for interaction between the 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 (HTR) in mice is evoked by 5-hydroxytryptamine (5-HT, serotonin), the 5-HT precursor, the directly acting non-selective 5-HT receptor agonists and 5-HT releasers. METHOD: In order to determine the GABAergic and 5-HTergic involvement in the induction of WDS behavior in rats the study was taken up to investigate the effect of clomipramine a 5HT depletor, pretreatment on sodium valproate, dexfenfluramine and 5-hydroxytrytamine (5-HTP) induced WDS behavior in rats. OBSERVATION: It was observed that Valproate in the dose range of 200-500mg/kg induced dose dependent WDS in rats. RESULTS: It was observed that pretreatment with PCPA significantly decreased the number of head and whole body shakes in rats caused by valproate and dexfenfluramine. This indicates that the induction of WDS behavior by valproate depends on the availability of brain 5HT and that valproate acts indirectly by releasing 5HT from the 5HTergic neurons.