The effect of leptin on prepulse inhibition in a developmental model of schizophrenia

Post-weaning social isolation is a developmental animal model of schizophrenia. Impairment of prepulse inhibition (PPI), possibly due to increased activity of the mesolimbic dopaminergic system, has frequently been reported in this model. There are some reports of increased level of leptin in schizophrenic patients. It has been shown that intracerebroventricular (ICV) injection of leptin decreases dopamine in the nucleus accumbens of rats. Here we investigated the effect of leptin on PPI impairment following social isolation. Five groups of Sprague-Dawley rats were reared post weaning in social or isolated conditions for 14 weeks. PPI was measured before treatment in week 12, and after ICV injection of vehicle or different doses of leptin (1, 5, and 10 μg/5 μl) in week 14. Results showed reduced PPI in untreated isolated compared to socially-reared rats in week 12 (p = 0.009), but not in week 14 (p = 0.45). Results also showed that leptin dose-dependently increased the basal PPI in isolated rats compared to vehicle, that was significant at a dose of 10 μg (p = 0.002). A considerable but non-significant effect of treatment with leptin on startle response (p = 0.13) was seen. In conclusion, our results reveal that leptin significantly increases PPI in socially-isolated rats. The findings of this study suggest possible antipsychotic properties for leptin. We suggest further studies on the possible disruption of leptin signaling in schizophrenia, and also the possible interaction of leptin with therapeutic effects of second generation antipsychotics.