Effect of prenatal exposure to diazepam on brain GABA(A) receptor mRNA levels in rats examined at late fetal or adult ages.

This study tested the hypotheses that in utero exposure to diazepam (DZ): (1) exerts long-lasting effects on GABA(A) receptor function by altering GABA(A) receptor subunit mRNA levels in specific brain regions of adult animals and/or (2) alters GABA(A) subunit mRNA expression in exposed fetuses. We assayed levels of mRNAs encoding several of the most predominant GABA(A) receptor subunits as well as cyclophilin mRNA. Analysis of mRNA levels in the cortex in adults showed that only gamma2S mRNA levels varied significantly with prenatal drug exposure, an effect unrelated to DZ action to the GABA(A) receptor. Analysis in fetuses indicated that mRNA levels varied as a function of both fetal sex and fetal drug environment. Irrespective of sex, DZ exposure increased both alpha1 and cyclophilin mRNAs in fetal brainstem whereas the mRNA levels of gamma2S were increased and decreased, respectively, in the telencephalon and hypothalamus of DZ-exposed fetuses.