EVALUATION OF A RAT MODEL OF VALPROATE-INDUCED OBESITY

Long-term treatment with the anticonvulsant valproate (VPA) leads to w ell-documented weight gain and obesity in humans. In an attempt to dev elop an animal model of this condition, adult rats were given VPA 20 g /kg (high-dose) or 2 g/kg (low-dose) in their daily feeding or orally 120 mg/kg body weight/day in two divided doses, and food intake and bo dy weight were assessed. Valproate resulted in lower body weights in a ll protocols. Food intake was lower (p<0.001) for rats receiving high- dose VPA than for controls. Feed efficiency (change in weight divided by cumulative food intake for that period) was lower than that of cont rols for both high (p<0.0001) and low doses (NS). Metabolic rate and p hysical activity were not different between control and VPA animals, a lthough decreased food intake would be expected to decrease metabolic rate. Valproate failed to produce obesity in rats in any treatment per iod. For reasons that are unclear, rats do not appear to be suitable a s a model to study this adverse side effect of VPA in humans with epil epsy.