Startle gating after frontal cortex or hippocampal lesions in adult rats

Abstract

Sensorimotor gating of the startle reflex is impaired in humans with schizophrenia and in rats after mesolimbic D2 dopamine receptor activation. The loss of startle gating after D2 activation in rats has been used as an animal model of impaired sensorimotor gating in schizophrenia, because the ability of antipsychoties to restore startle gating in D2-activated rats conelates significantly (R-0.991) with clinical antipsychotic potency. Substantial evidence indicates that the pathophysiology of schizophrenia includes structural and functional deficits in prefrontal and temporal regions, particularly the dorsolateral prefrontal cortex and the hippocampus and parahippocampal gyms. in the present study, we assessed startle gating in adult rats after ibotenic acid lesions of the medial prefrontal cortex (MPFC) or ventral hippocampus. MPFC-lesionad rats exhibited normal startle amplitude and normal sensorimotor gating as reflected by prepulse inhibition (PPl) of the startle reflex. Ventral hippocampus-lesioued rats exhibited significantly elevated startle amplitude and reduced PPl. Subthreshold doses of the mixed DI/D2 agonist apomorphine that did not significantly reduce PPl in sham-lesioued rats significantly disrupted PPl in both MPFCand ventral hippocamlms-lesioned rats. Our data indicates that cell damage in the ventral hippocampus reduces sensorimotor gating, and that damage to either the MPFC or ventral hippocampus enhances the sensitivity to the sensorimotor gating-disruptive effects of dopamine receptor activation. These data may have direct relevance to the neural substrates of impaired sensorimotor gating in schizophrenia, a disorder associated with dysfunction in frontal cortex and hippocampus.