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

✍ Scribed by David J. Stone; John P. Walsh; Ronnie Sebro; Renna Stevens; Harry Pantazopolous; Francine M. Benes

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 916 KB
• Volume: 11
• Category: Article
• ISSN: 1050-9631
• DOI: 10.1002/hipo.1066

✦ Synopsis

Abstract

Several lines of evidence have implicated prenatal stress and the hippocampal 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 vehicle to establish three study groups: VVV, receiving vehicle at all three time points; VCC, receiving vehicle prenatally and CORT at both postnatal timepoints; and CCC, receiving CORT at all three timepoints. Animals were sacrificed at either 24 h or 5 days after final injection and examined for mRNA levels of GAD~65~, GAD~67~, and the GABA~A~ receptor subunits α~2~ and γ~2~. At 24 h, GAD~65~ mRNA was decreased in CA1, CA2, CA4, and dentate gyrus (DG) of VCC rats; this effect was either decreased or reversed in CCC‐treated animals. No effect was detected in GAD~67~ mRNA at 24 h. At 5 days, CORT treatment increased GAD~67~ mRNA levels in CA1, CA3, and DG. Prenatal treatment with CORT was associated with increased responsiveness only in CA3 and DG. For the GABA~A~ receptor, α~2~ subunit mRNA did not show any change in response to CORT treatment, while that for the γ~2~ subunit was decreased in CA2 of both VCC‐ and CCC‐treated animals. Consistent with γ~2~ subunit mRNA decreases, benzodiazepine (BZ) receptor binding activity was decreased in CA2 with CORT treatment. Prenatal CORT exposure neither increased nor decreased this effect. These results demonstrate that CORT administration is associated with a complex regulation of mRNA expression for pre‐ and postnatal aspects of the hippocampal GABA system. Under these conditions, prenatal exposure to CORT may sensitize some of these effects, but does not fundamentally alter the nature of this response. Hippocampus 2001;11:492–507. © 2001 Wiley‐Liss, Inc.