ADAPTIVE-CHANGES OF DOPAMINE-D(2) RECEPTORS IN RAT-BRAIN FOLLOWING ETHANOL WITHDRAWAL - A QUANTITATIVE AUTORADIOGRAPHIC INVESTIGATION

The effect of subchronic treatment with two doses of ethanol (5 and 10 vol% drinking fluid) on the density of dopamine-D2 receptors was investigated at two different phases of withdrawal, namely 24 h and 5 days after the cessation of the ethanol application. The number of dopamine-D2 receptors was affected in regions receiving projections from both the substantia nigra as well as the ventral tegmentum. Twenty-four hours after the replacement of the ethanol solution by water, a dose-dependent decrease of D2 receptors was found in all regions (N. caudatus dorsalis, medialis and ventralis, N. accumbens lateralis and medialis, tuberculum olfactorium) and most of the analyzed planes [interaural 7.7-10.2 according to the atlas of Paxinos and Watson (35)]. At day 5 of withdrawal, the number of dopamine-D2 receptors of the animals treated with 5 vol% ethanol reached the level of water controls in most planes. In contrast, two- to three-fold higher numbers were detected in animals treated with the higher dose. Only in the most caudal parts of the investigated regions, was the number of receptors decreased with the higher dose. The mesocorticolimbic system seems to be less sensitive to the effects of ethanol than the nigrostriatal neurones. The findings of the present study suggest an increased activity of dopaminergic neurons with an adaptive reduction of dopamine-D2 receptors during the subchronic treatment with ethanol during the first day(s) of withdrawal. This phase is followed by a reduced turnover rate for up to 7 days (21). The reduced activity of dopaminergic neurones induces a compensatory increase of the number of receptors. The recovery of dopamine neurones during the late phase of withdrawal takes place when the number of receptors are still increased. The possible clinical implications are discussed.