Effects of clozapine (CLZ) on reduced prepulse inhibition (PPI) after neonatal excitotoxic lesion of the ventral thalamus in pubertal and adult rats

Introduction: Growing evidence has indicated the role of the thalamus in schizophrenia. The aim of this study was to investigate the effect of neonatal excitotoxic lesions in ventral thalamus on sensorimotor gating in Sprague-Dawley rats. Methods: At postnatal day (PD 7) male pubs were bilaterally infused into ventral thalamus with ibotenic acid (IBA) or artificial cerebrospinal fluid (controls). Measurements of PPI were performed in puberty and adulthood. Results: IBA animals showed lower PPI (p<0.001) levels in comparison to controls. The extent of ventral thalamic lesions correlated negatively with PPI levels (p<0.001), and in comparison to corollary lesions caused by cannulation only the extent of ventral thalamic lesions exert a predominantly PPI lowering effect. PPI deficits in IBA animals were observed at PD 43 and increased significantly after puberty without reaching control levels. Acute or subchronic CLZ (5 or 10mg/kg i.p.) treatment did not significantly increase PPI in IBA rats. Conclusions: Using a neurodevelopmental model, these results support our view that the ventral thalamus plays a role in regulating sensorimotor gating and may be involved in PPI deficits observed in schizophrenia. However, the missing effectiveness of CLZ on ventral thalamus-related PPI deficits needs to be further investigated.