Reduced gene expression for dopamine biosynthesis and transport in midbrain neurons of adult male rats exposed prenatally to ethanol

Background: Prenatal ethanol exposure affects brain dopaminergic neuronal s ystems, and many of these alterations are permanent. Methods: The primary objective of this study was to determine the effects o f prenatal ethanol exposure on adult mRNA expression for two key regulatory proteins in the mesolimbic and nigrostriatal dopaminergic cell groups whic h mediate behavioral responses to alcohol and other drugs of abuse: tyrosin e hydroxylase (TH) and dopamine transporter (DAT) in the substantia nigra p ars compacta (SNpc) and ventral tegmental area (VTA). To also address the e ffects on noradrenergic regulation, we quantitated mRNA expression for TH a nd norepinephrine transporter (NET) in the noradrenergic loci of the locus coeruleus(LC) Results: Daily dietary ethanol consumption by female Sprague-Dawley rats fo r 3 weeks before, and continuing throughout, pregnancy decreased both DAT ( similar to 68%, p < 0.002) and TH (similar to 45%, p < 0.002) mRNA expressi on in the VTA of adult male offspring. This prenatal exposure also suppress ed DAT mRNA expression in the SNpc (similar to 81%; p < 0.03), although TH mRNA expression in this region was not significantly altered. Prenatal etha nol exposure did not alter significantly either TH or NET mRNA expression i n the LC of adult male offspring, which suggests that this brain catecholam inergic response may be limited to DA neurons. Conclusion: These results demonstrated that prenatal maternal ethanol consu mption suppresses mRNA expression for important regulatory proteins in the mesolimbic and nigrostriatal dopaminergic systems of adult male rat offspri ng. These persistent prenatal ethanol-induced changes in mRNA expression ma y thus contribute to the persistent effects of fetal ethanol exposure on th e diverse behavioral and/or metabolic responses meditated by the mesolimbic and nigrostriatal dopaminergic systems in the adult.