Effects of pre- and postnatal corticosterone exposure on the rat hippocampal GABA system

Several lines of evidence have implicated prenatal stress and the hippocamp al GABA system in the pathophysiology of schizophrenia, and prenatal stress is believed to increase the risk for schizophrenia through alterations of this neurotransmitter. To explore this hypothesis, we treated male rats pre - and/or postnatally (P48 and P60) with either corticosterone (CORT) or veh icle to establish three study groups: VVV, receiving vehicle at all three t ime points; VCC, receiving vehicle prenatally and CORT at both postnatal ti mepoints; and CCC, receiving CORT at all three timepoints. Animals were sac rificed at either 24 h or 5 days after final injection and examined for mRN A levels of GAD(65), GAD(67), and the GABA, receptor subunits alpha (2) and gamma (2). At 24 h, GAD(65) mRNA was decreased in CA1, CA2, CA4, and denta te gyrus (DG) of VCC rats; this effect was either decreased or reversed in CCC-treated animals. No effect was detected in GAD67 mRNA at 24 h. At 5 day s, CORT treatment increased GAD67 mRNA levels in CA1, CA3, and DG. Prenatal treatment with CORT was associated with increased responsiveness only in C A3 and DG. For the GABA(A) receptor, a. subunit mRNA did not show any chang e in response to CORT treatment, while that for the gamma (2) subunit was d ecreased in CA2 of both VCC- and CCC-treated animals. Consistent with gamma (2) subunit mRNA decreases, benzodiazepine (BZ) receptor binding activity was decreased in CA2 with CORT treatment. Prenatal CORT exposure neither in creased nor decreased this effect. These results demonstrate that CORT admi nistration is associated with a complex regulation of mRNA expression for p re- and postnatal aspects of the hippocampal GABA system. Under these condi tions, prenatal exposure to CORT may sensitize some of these effects, but d oes not fundamentally alter the nature of this response. (C) 2001 Wiley-Lis s, Inc.