NEONATAL HIPPOCAMPAL LESION MODEL OF SCHIZOPHRENIA IN RATS - SEX-DIFFERENCES AND PERSISTENCE OF EFFECTS INTO MATURITY

A neurodevelopmental model of schizophrenia in rats has recently been proposed employing neonatal hippocampal lesions. The present study fur ther characterizes this model by investigating the long-term effects o f neonatal hippocampal lesions up to 100 days after birth, in male rat s as well as female rats. Lesions were performed on postnatal day seve n (PD 7). Our results showed that neonatal hippocampal lesions produce d enhanced hyperlocomotory behavior during spontaneous locomotion and after amphetamine administration. In general, these hyperlocomotory ef fects were more apparent and appeared earlier in male lesioned animals than in female lesioned animals. Lesioned males exhibited a significa nt increase in spontaneous locomotion on PD 56 and PD 100, whereas les ioned females showed a significant increase in spontaneous locomotion on PD 100 only. On all test days, amphetamine injection produced a sig nificant enhancement of hyperlocomotion in lesioned males and females vs. control; this effect was more pronounced in males. No changes in r eceptor binding characteristics (D-2, 5HT(2A) and neurotensin) were fo und between lesioned and sham-operated animals of either sex. These da ta lend support to the validity of the neonatal hippocampal lesion mod el of schizophrenia. (C) 1998 Wiley-Liss, Inc.