Reduction of Prepulse Inhibition (PPI) after neonatal excitotoxic lesion of the ventral thalamus in pubertal and adult rats.

Background: Growing evidence indicates the role of the thalamus in schizophrenia. The ventral part of the thalamus has been investigated in a few post-mortem studies, suggesting a possible neurodevelopmental etiology of the reduced neuron number.

Methods: Here we adapt a neurodevelopmental animal model, the neonatal excitotoxic brain lesion, to the ventral thalamus (VT) of Sprague-Dawley rats.

Acute or subchronic clozapine treatment does not ameliorate prepulse inhibition (PPI) deficits in CPB-K mice with low levels of hippocampal NMDA receptor density.

Introduction: The hypo-glutamatergic hypothesis of schizophrenia is based on clinical similarities between schizophrenia and phencyclidine (PCP)-induced psychosis in mentally healthy humans. Sensorimotor gating, as measured by prepulse inhibition (PPI) of the acoustic startle response (ASR), is impaired in schizophrenic patients. In animals, noncompetitive N-methyl-D: -aspartate (NMDA) antagonists such as PCP disrupt PPI in a way that resembles the defect seen in schizophrenia.

Prepulse inhibition is different in two inbred mouse strains (CPB-K and BALB/cJ) with different hippocampal NMDA receptor densities.

Objective: The hypo-glutamatergic hypothesis of schizophrenia is not only based on the phencyclidine-(PCP)-induced psychosis in mentally healthy humans but also on studies with schizophrenic patients showing deficits in post mortem hippocampal N-methyl-d-aspartate (NMDA) receptor gene expression and deficits in prepulse inhibition. The inbred mouse strains CPB-K and BALB/cJ display considerable differences in hippocampal NMDA receptor densities. Therefore, our working hypothesis was based on the assumption that the CPB-K mouse strain, which has a lower NMDA receptor density in hippocampal CA1, might be a possible animal model for schizophrenia.