A Comparison of mRNA Expression of Dopamine Receptors, Tyrosine Hydroxylase, and Dopamine Transporter in the Mesolimbic System of Rats with Different Levels of Alcohol Consumption

Abstract

Despite numerous studies, there is still no clear idea on the fine mechanisms of dysfunction of the brain dopamine system during the formation of alcohol dependence. In this work, we studied the expression of genes that encode tyrosine hydroxylase (TH), a key enzyme of dopamine synthesis, dopamine transporter (DAT), dopamine receptors of the second subtype (DRD2) in the midbrain, and dopamine receptors of the first and second subtypes (DRD1 and DRD2) in the striatum of rats that consumed alcohol from the 60th to 120th days of life in the “free choice” paradigm. The most pronounced changes, a decrease in mRNA expression of DRD1 and DRD2 in the striatum, as well as DAT and TH in the midbrain, were observed in animals with a growing preference for alcohol compared to a group of rats that controlled consumption at a constantly low level. In animals with initially stable high levels of alcohol preference, a decrease in the relative expression level of DRD1 and DRD2 mRNA in the striatum was found, while there was no difference in the expression of DAT and TH mRNA in the midbrain. The expression level of DRD2 mRNA in the midbrain did not differ in all the studied groups. These data suggest that changes in the expression of mRNA of DRD1 and DRD2 in the striatum do not depend on the initial alcohol preference and are determined by the level of alcohol intoxication, while the decrease in the level of TH and DAT mRNA in the midbrain may be one of the mech-anisms of loss of control over consumption.