Fm. Hanlon et Rj. Sutherland, Changes in adult brain and behavior caused by neonatal limbic damage: implications for the etiology of schizophrenia, BEH BRA RES, 107(1-2), 2000, pp. 71-83
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.