Acoustic startle responses of rats with cerebral developmental abnormalities: implications for schizophrenia

Mounting evidence suggests involvement of prenatal factors in the pathogenesis of schizophrenia. The objective of the present study was to provide evidence for the hypothesis on schizophrenia that abnormal fetal brain development leads to impaired sensorimotor gating of acoustic startle stimuli. To this purpose, pregnant rats were treated with methylazoxymethanol acetate on one of four subsequent days of gestation, from E9 to E12. These procedures inhibit early stages of cortical proliferation in the foetuses, resulting in adult brain abnormalities that were mainly found in the entorhinal region. At the adult age, habituation andprepulse inhibition (PPI) of startle responses to acoustic stimuli were investigated. Our results show impaired habituation and PPI in rats treated at embryonic days 10 and 11. It is concluded that sensorimotor gating deficits can result from a developmental abnormality involving the entorhinal region, supporting the hypothesis that similar deficits, often observed in schizophrenic subjects, may be the result of entorhinal cortex dysfunction.