Changes in adult brain and behavior caused by neonatal limbic damage: implications for the etiology of schizophrenia

We tested the hypothesis that limbic damage in early development can cause aberrant maturation of brain structures known to be abnormal in adult schizophrenics: the hippocampus, prefrontal cortex, ventricles, and forebrain dopamine systems. We measured brain morphology, locomotor response to apomorphine, and cognitive processes in adult rats which received electrolytic damage to amygdala or hippocampus 48 h after birth. The behavioral measurements involved tasks which depend upon the integrity of the hippocampus or prefrontal cortex, and a task sensitive to forebrain dopamine system activation. The tasks included place navigation, egocentric spatial ability, and apomorphine-induced locomotion. The rats with lesions showed poor performance on the place navigation and egocentric spatial tasks and more apomorphine-induced locomotion after puberty than the sham lesion group. Regardless of lesion location, the adult rats showed smaller amygdalae and hippocampi, and larger lateral ventricles. Analyzing the lesion and sham rats together, adult amygdala volume was found to be positively correlated with cerebral cortex, prefrontal cortex, and hippocampal volumes and place navigation performance, and was negatively correlated with lateral ventricle volume. This study contributes to our understanding of the pathogenesis of schizophrenia by showing that early damage to limbic structures produced behavioral, morphological, and neuropharmacological abnormalities related to pathology in adult schizophrenics. (C) 2000 Elsevier Science B.V. All rights reserved.