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 schiz ophrenics: the hippocampus, prefrontal cortex, ventricles, and forebrain do pamine systems. We measured brain morphology, locomotor response to apomorp hine, and cognitive processes in adult rats which received electrolytic dam age to amygdala or hippocampus 48 h after birth. The behavioral measurement s involved tasks which depend upon the integrity of the hippocampus or pref rontal cortex, and a task sensitive to forebrain dopamine system activation . The tasks included place navigation, egocentric spatial ability, and apom orphine-induced locomotion. The rats with lesions showed poor performance o n the place navigation and egocentric spatial tasks and more apomorphine-in duced locomotion after puberty than the sham lesion group. Regardless of le sion location, the adult rats showed smaller amygdalae and hippocampi, and larger lateral ventricles. Analyzing the lesion and sham rats together, adu lt amygdala volume was found to be positively correlated with cerebral cort ex, prefrontal cortex, and hippocampal volumes and place navigation perform ance, and was negatively correlated with lateral ventricle volume. This stu dy contributes to our understanding of the pathogenesis of schizophrenia by showing that early damage to limbic structures produced behavioral, morpho logical, and neuropharmacological abnormalities related to pathology in adu lt schizophrenics. (C) 2000 Elsevier Science B.V. All rights reserved.