AMPHETAMINE-INDUCED C-FOS MESSENGER-RNA EXPRESSION IS ALTERED IN RATSWITH NEONATAL VENTRAL HIPPOCAMPAL DAMAGE

To further characterize the mechanisms underlying enhanced dopamine-re lated behaviors expressed during adulthood in rats with neonatal excit otoxic ventral hippocampal (VH) damage, we studied the expression of c -fos mRNA in these rats after a single saline or amphetamine (AMPH) (1 0 mg/kg, i.p.) injection using in situ hybridization. The VH of rat pu ps was lesioned with ibotenic acid on postnatal day 7 (PD7). At the ag e of 90 days, rats were challenged with AMPH or saline, and the expres sion of c-fos mRNA using an oligonucleotide probe was assessed 30, 90, and 180 min later. AMPH significantly increased c-fos mRNA expression in medial prefrontal cortex, piriform cor-tex, cingulate cortex, sept al region, and dorsolateral and ventromedial striatum in control and l esioned rats. However, this response to AMPH was attenuated 30 min aft er AMPH injection in all of these regions in the lesioned as compared to the sham-operated rats. No significant changes were seen at other t ime points. These results indicate that the neonatal VH lesion alters time-dependent intracellular signal transduction mechanisms measured b y AMPH-induced c-fos mRNA expression in cortical and subcortical brain regions. Changes in c-fos mRNA expression in this putative animal mod el of schizophrenia may have implications for long-term alterations in cellular phenotype because of altered regulation of certain target ge nes. (C) 1996 Wiley-Liss, Inc.