INCREASED SENSITIVITY TO THE SENSORIMOTOR GATING-DISRUPTIVE EFFECTS OF APOMORPHINE AFTER LESIONS OF MEDIAL PREFRONTAL CORTEX OR VENTRAL HIPPOCAMPUS IN ADULT-RATS

Sensorimotor gating of the startle reflex is impaired in humans with s chizophrenia and in rats after mesolimbic D-2 dopamine receptor activa tion. The loss of startle gating after D-2 activation in rats has been used as an animal model of impaired sensorimotor gating in schizophre nia, because the ability of antipsychotics to restore startle gating i n D-2-activated rats correlates significantly with antipsychotic clini cal potency. Substantial evidence indicates that the pathophysiology o f schizophrenia includes structural and functional deficits in prefron tal and temporal regions, particularly the dorsolateral prefrontal cor tex and the hippocampus and parahippocampal gyrus. The present : study assessed startle gating in adult rats after ibotenic acid lesions of the medial prefrontal cortex or ventral hippocampus. Medial prefrontal cortex lesioned rats exhibited normal startle amplitude and normal se nsorimotor gating, as reflected by prepulse inhibition (PPI) of the st artle reflex. Hippocampus lesioned rats exhibited elevated startle amp litude, and similar to rats with medial prefrontal cortex lesions, did not show significant changes in basal PPI. Low doses. of the mixed do pamine agonist apomorphine did not significantly reduce PPI in sham le sioned rats, but significantly disrupted PPI in both medial prefrontal cortex and ventral hippo-campus lesioned rats. These data are consist ent with the hypothesis that cell damage in frontal and temporal corte x increases the sensitivity to the sensorimotor gating-disruptive effe cts of dopamine receptor activation.