Prenatal Exposure to the Pesticide Dieldrin or the GABAA Receptor Antagonist Bicuculline Differentially Alters Expression of GABAA Receptor Subunit mRNAs in Fetal Rat Brainstem

Abstract

We have previously shown that GABA acts as a trophic signal for monoamine neurons in embryonic day 14 (E14) rat brainstem cultures [Liu et al., J Neurosci 1997a;17:2420–2428]. The organochlorine pesticide dieldrin and the classical GABA_A receptor antagonist bicuculline interfere with the trophic actions of GABA and alter expression of several GABA_A receptor subunit mRNA transcripts in these cultures [Liu et al., J Neurosci Res 1997b;49:645–653]. In the present study, we investigated whether prenatal exposure to dieldrin or bicuculline from E12–17 would alter mRNA expression of α1, β3, γ1, γ2S and γ2L GABA_A receptor subunits in fetal (E17) rat brainstem using competitive RT-PCR to absolutely quantify these transcripts. The effects of dieldrin and bicuculline on expression of GABA_A receptor subunit transcripts were similar across subunits. Dieldrin and bicuculline decreased expression of α1, β3 and γ1 transcripts compared to vehicle-injected controls, but did not significantly alter expression of γ2S and γ2L transcripts. Taken together, these studies indicate that in utero exposure to organochlorine pesticides acting as GABA_A receptor antagonists may alter the expression and subunit composition of developing GABA_A receptors. If these changes persist, they could have long-lasting effects on developing GABAergic neural circuitry, GABA_A receptor function and GABA-mediated behaviors.