EFFECT OF ETHANOL DRINKING ON THE GENE-EXPRESSION OF OPIOID RECEPTORS, ENKEPHALINASE, AND ANGIOTENSIN-CONVERTING ENZYME IN 2 INBRED MICE STRAINS

There is convincing evidence that genetic factors contribute to the pr edisposition to alcoholism. In this respect, alcohol-preferring (like C57BL/6 mice) and alcohol-avoiding lines (like DBA/2 mice) of animals served as models in the search for neurobiological substrates of exces sive ethanol consumption. One of the systems that is thought to be ass ociated with the incidence of alcoholism is the endogenous opioid syst em. In the first experiment, basal mRNA levels of mu- and delta-opioid receptors, and of opioid-degrading enzymes enkephalinase (neutral end opeptidase 24.11; NEP) and angiotensin-converting enzyme (ACE) in the brain regions of C57BL/6 and DBA/2 mice did not reveal genetically det ermined differences in these parameters between the two strains. Furth ermore, in the brain regions studied, the corresponding enzyme activit ies of NEP and ACE did not differ significantly between the lines of m ice, except for a higher NEP activity in the striatum and olfactory bu lb of DBA/2 mice(p < 0.01). In the second experiment, C57BL/6 and DBA/ 2 mice were offered a free choice between water and 10% ethanol soluti on for 4 weeks and were killed thereafter; from another group, ethanol was removed for 3 days and from a third group ethanol was removed for 3 weeks before killing. In the striatum, a highly significant increas e in the ACE mRNA amount was detected after 3 weeks of removal of etha nol in C57BL/6 mice, whereas in DBA/2 mice the delta-opioid receptor m RNA level was increased at this time when compared with the correspond ing ethanol treatment group. The most striking changes were seen in th e hypothalamus, where p-opioid receptor, ACE, and NEP mRNA amounts mar kedly decreased after ethanol treatment in both strains. Thus, chronic ethanol intake caused significant changes in the gene expression of d istinct components of the endogenous opioid system. These findings fur ther underline an involvement of the opioid system in the effects of e thanol.