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 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 coeruleus (LC).


RESULTS
Daily dietary ethanol consumption by female Sprague-Dawley rats for 3 weeks before, and continuing throughout, pregnancy decreased both DAT (approximately 68%,p < 0.002) and TH (approximately 45%,p < 0.002) mRNA expression in the VTA of adult male offspring. This prenatal exposure also suppressed DAT mRNA expression in the SNpc (approximately 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.


CONCLUSIONS
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 mediated by the mesolimbic and nigrostriatal dopaminergic systems in the adult.
Szot
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P
Geriatric Research, Education and Clinical Center, Puget Sound Health Care System, and the Department of Psychiatry, University of Washington, Seattle 98108, USA. szot@u.washington.edu
White
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Veith
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Rasmussen
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D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D004298:Dopamine / Q000096:biosynthesis*; D050483:Dopamine Plasma Membrane Transport Proteins; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009638:Norepinephrine / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects* / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D002352:Carrier Proteins; D002492:Central Nervous System Depressants; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493216:Slc6a3 protein, rat; D000431:Ethanol; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D009638:Norepinephrine