Alcohol consumption alters monoamine oxidase activities in brain structures: relation to ethanol craving

In spite of numerous biochemical studies the role of brain monoamine oxidase (MAO, EC 1.4, 3.4) in the mechanisms of central alcohol action and the pathogenesis of alcoholism remains unclear. The possible reason of that is the highly heterogeneous distribution of the enzyme in a brain and the different direction of alcohol-induced changes of MAO in various morphological structures. Therefore we used the histochemical approach for examination of the effect of chronic alcohol consumption on MAO A and B activities in definite brain structures: various types of aminergic neurons, glial cells and blood capillaries.

For 6 months 180 inbred male rats consumed 15% ethanol as the only source of drinking (mean alcohol consumption was 6 g/kg/day). On the 5-6th months of the experiment animals with maximal (ethanol preferring, EP) or minimal (water preferring, WP) alcohol craving were chosen by testing for free choice between 15% (v/v) ethanol solution and water (3 times, during 2 days, at 2-week intervals). The animals chosen were sacrificed and brain samples were studied by our quantitative histochemical method (23). It was found, that chronic ethanol consumption induced dramatic disturbances in MAO activities in the brain structures strongly depending on the alcohol preference of animals. The total MAO activity in WP rats decreased or remained unchanged, but in EP rats it dramatically increased, especially in neurons of n. raphe pontis and n. raphe dorsalis (1.198 +/- 0.028 and 1.268 +/- 0.018 units as compared to control values 0.594 +/- 0.008 and 0.804 +/- 0.011 units; p < 0.001). MAO A activity in all brain structures containing both forms of the enzyme was increased, especially in EP rats: up to 3 times in neurons of the n. raphe pontis from 0.134 +/- 0.003 units in control to 0.541 +/- 0.013 units; p < 0.001). At the same time in the neurons containing only MAO A activity (n. olivaris superior and n. subcoeruleus) it significantly decreased, especially in WP animals. MAO B activity was reduced in the brain structures of WP rats, but activated or unchanged in EP rats. In all the structures studied the MAO B activity was significantly higher in EP, as compared to WP animals (f.e. in astrocytes: 0.314 +/- 0.012 and 0.200 +/- 0.012 units accordingly, p < 0.001). Despite the significant differences in the degree and direction of the changes in the activity of the MAO forms in rats with different alcohol craving, the calculated share of MAO A in the total MAO activity was regularly increased in all structures studied both in EP and WP animals; the share of MAO B activity accordingly decreased.

Chronic alcohol consumption induces the great disturbances in brain MAO activity and isozyme composition following chronic ethanol consumption, strongly depending of the alcohol craving of the animals. It indicates the involvement of the enzyme in the mechanisms of central alcohol action.