Influence of chronic alcohol consumption on histaminergic neurons of the rat brain.

AIMS: To clarify the effect of chronic alcohol consumption on the brain histaminergic neurons in rats. METHODS: Male Wistar rats were given 20% ethanol as the only source of drinking during 6 months, control rats had a free access to water. The samples of hypothalamus were prepared for light and electron microscopy accompanied by morphometry to examine the brain histaminergic neurons of E2 group. RESULTS: Chronic ethanol consumption increased the amount of histologically abnormal forms of histaminergic neurons and decreased the whole amount of E2 histaminergic neurons (for 5%). The neuron bodies and nuclei increased in size and sphericity, the nuclear/cytoplasmic ratio decreased by 15%. The ultrastructural changes in histaminergic neurons demonstrate the activation of their nuclear apparatus, both destruction and hypertrophy and hyperplasia of organelles, especially lysosomes. Chronic ethanol consumption induces the disturbances in cytoplasmic enzymes of neurons: increases the activity of type B monoamine oxidase, dehydrogenases of lactate and NADH and, especially, marker enzyme of lysosomes acid phosphatase as well as inhibits the activity of dehydrogenases of succinate and glucose-6-phosphate. CONCLUSION: Chronic alcohol consumption affects significantly the structure and metabolism of the brain histaminergic neurons, demonstrating both the neurotoxic effect of ethanol and processes of adaptation in those neurons, necessary for their survival.

Acetate-dependent mechanisms of inborn tolerance to ethanol.

AIMS: To clarify the role of acetate in neurochemical mechanisms of the initial (inborn) tolerance to ethanol. METHODS: Rats with low and high inborn tolerance to hypnotic effect of ethanol were used. In the brain region homogenates (frontal and parietal cortex, hypothalamus, striatum, medulla oblongata) and brain cortex synaptosomes, the levels of acetate, acetyl-CoA, acetylcholine (AcH), the activity of pyruvate dehydrogenase (PDG) and acetyl-CoA synthetase were examined. RESULTS: It has been found that brain cortex of rats with high tolerance to hypnotic effect of ethanol have higher level of acetate and activity of acetyl-CoA synthetase, but lower level of acetyl-СCoA and activity of PDG. In brain cortex synaptosomes of tolerant rats, the pyruvate oxidation rate as well as the content of acetyl-CoA and AcH synthesis were lower when compared with intolerant animals. The addition of acetate into the medium significantly increased the AcH synthesis in synaptosomes of tolerant, but not of intolerant animals. Calcium ions stimulated the AcH release from synaptosomes twice as high in tolerant as in intolerant animals. Acetate eliminated the stimulating effect of calcium ions upon the release of AcH in synaptosomes of intolerant rats, but not in tolerant animals. As a result, the quantum release of AcH from synaptosomes in the presence of acetate was 6.5 times higher in tolerant when compared with intolerant rats. CONCLUSION: The brain cortex of rats with high inborn tolerance to hypnotic effect of ethanol can better utilize acetate for the acetyl-CoA and AcH synthesis, as well as being resistant to inhibitory effect of acetate to calcium-stimulated release of AcH. It indicates the metabolic and cholinergic mechanisms of the initial tolerance to ethanol.