Effect of ethanol consumption on the expression of the tyrosine hydroxylase gene in rat brain and adrenals

Abstract

After chronic alcoholization for 9 months with increased doses of ethanol, the tyrosine hydroxylase gene in the brain and adrenals of rats is expressed at different levels depending on the intensity of the desire for alcohol. Key Words: ethanol; alcohol dependence; tyrosine hydroxylase; gene expressionResults of experimental and clinical studies led us to conclusion that a leading role in the establishment of 'alcohol dependence is played by functional changes in the catecholamine neurotransmitter system in the brain. Enzymes, particularly monoamine oxidase, dopamine-I~-hydroxylase, tyrosine hydroxylase, and catecholortho-methyltransferase, play an important role in the regulation of catecholamine metabolism. There is a large body of evidence that the activities of these enzymes are altered during prolonged alcoholization [1,3,5], and some of these changes may be implicated in the development of alcohol dependence [3,[6][7][8].Tyrosine hydroxylase (TH), the key enzyme in catecholamine synthesis, converts the amino acid tyrosine into the dopamine precursor dihydroxyphenylalanine, and alterations in the enzyme activity, particularly if sustained, may strongly determine the function of the catecholamine system, However, the neurochemical nature of shifts in the activity of enzymes involved in catecholamine metabolism during prolonged alcoholization has not been ascertained. These shifts may be caused by changes in the transcriptional activity of genes coding for the enzyme.Alcohol dependence does not necessarily result from long-lasting alcohol consumption and, moreLaboratory of Psychopharmacology, Institute of N~'cology, State Research Center for Psychiahy and Narcology, Ministry of Health of the Russian Federation, Moscow over, the risk of alcoholism does not correlate with the level of initial alcohol motivation. Presumably, individual risk of alcoholism is linked to a long-term regulation of the activities of catecholamine-metabolizing enzymes, including TH, at the level of the nerve cell genome.The objectives of the present study were to evaluate the effect of chronic alcohol intoxication on the expression of the TH gene in the brain and adrenals of experimental animals and to examine changes in the expression of this gene in these organs in relation to the degree of pathological desire for alcohol. MATERIALS AND METHODSMale Wistar rats aged 3 months were used. They received ethanol in increasing concentrations as the only source of liquid: 5% ethanol solution during the 1st week, 10% solution during the 2nd, and 15% solution during the 3rd week and, until the end of the 9-month period of alcoholization. Then the animals had free choice between water and 15% ethanol solution for 2 weeks. Ethanol consumption during these 2 weeks was calculated from the following formula:C=VJVli , where V t is the volume of 15% ethanol consumed per day and V n is the total volume of liquid consumed per day. Ethanol consumption for each rat was calculated as the mean of daily C values over the 2-week period.