Reduced Gene Expression for Dopamine Biosynthesis and Transport in Midbrain Neurons of Adult Male Rats Exposed Prenatally to Ethanol

Abstract

Background: Prenatal ethanol exposure affects brain dopaminergic neuronal systems, and many of these alterations are permanent. Methods: The primary objective of this study was to determine the effects of prenatal ethanol exposure on adult mRNA expression for two key regulatory proteins in the mesolimbic and nigrostriatal dopaminergic cell groups which mediate behavioral responses to alcohol and other drugs of abuse: tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). To also address the effects on noradrenergic regulation, we quantitated mRNA expression for TH and norepinephrine transporter (NET) in the noradrenergic loci of the locus cocruleus (LC). Results: Daily dietary ethanol consumption by female Sprague-Dawley rats for 3 weeks before, and continuing throughout, pregnancy decreased both DAT (∼ 68%, p < 0.002) and TH (∼ 45%, p < 0.002) mRNA expression in the VTA of adult male offspring. This prenatal exposure also suppressed DAT mRNA expression in the SNpc (∼ 81%; p < 0.03), although TH mRNA expression in this region was not significantly altered. Prenatal ethanol exposure did not alter significantly either TH or NET mRNA expression in the LC of adult male offspring, which suggests that this brain catecholaminergic response may be limited to DA neurons. Conclusion: These results demonstrated that prenatal maternal ethanol consumption suppresses mRNA expression for important regulatory proteins in the mesolimbic and nigrostriatal dopaminergic systems of adult male rat offspring. These persistent prenatal ethanol-induced changes in mRNA expression may thus contribute to the persistent effects of fetal ethanol exposure on the diverse behavioral and/or metabolic responses meditated by the mesolimbic and nigrostriatal dopaminergic systems in the adult.