VALPROATE-INDUCED "WET DOG SHAKES" - A REPRODUCIBLE ANIMAL MODEL OF HUMAN COMPULSIVE BEHAVIOR : EFFECT OF ANTIDEPRESSANTS

Effect of serotonin re-uptake inhibitor, clomipramine (CMI) and selective serotonin re-uptake inhibitor, fluoxetine (FLX) (10 mg/ kg) administered intraperitoneally were tested on valproic acid (VPA) (300 mg/kg)-induced 'wet dog shakes' (WDSs) in rats, on day 1 and 29 (single and chronic administration of VPA). Single dose and chronic administration of VPA resulted in similar increase in the number of WDSs, demonstrating it's reproducibility. CMI and FLX pretreatment resulted in significant decreases in WDSs from day 1 to 29, where as the combination of FLX and CMI did not. Single dose CMI resulted in significant reduction in WDSs on day 1 compared to FLX and VPA conditions and chronic CMI produced significant reduction in WDSs compared to FLX, VPA and FLX plus CMI (p < 0.0005). Acute administration of FLX produced small but significant reduction of WDSs compared to VPA condition but chronic administration of FLX resulted in a substantial and significant decrease in WDSs. The profound decrease in WDSs with CMI suggests a predominant role for both serotonergic and anticholinergic activity, while more significant decrease of WDS on day 29 after CMI and FLX suggests a chronic receptor down regulation with either drug. The implications of these have been discussed in relation to mechanism of action of antidepressants in valproate-induced stereotyped behaviour in rats, representing a model of compulsive phenomenon seen in humans.