ACTIVATION OF PROGRAMMED CELL DEATH AND DEGENERATIVE CHANGES OF NEURONS OF MESOCORTICOLIMBIC DOPAMINERGIC SYSTEM AS A POSSIBLE CAUSE OF INHERITED ALCOHOL ADDICTION



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Abstract

It is known that the insufficiency of mesocorticolimbic dopaminergic system (MDS) lies in the basis of inherited alcohol addiction (IAA). The understanding of the pathogenesis of IAA is hampered by the absence of data on the number and volume of neuronal cell bodies in MDS and on the rate of their programmed cell death in the offspring of alcohol-dependent humans and animals. Morphological changes of neurons and macroglial cells of major MDS parts were studied in the offspring of intact Wistar rats (n=20) and in the offspring of female rats that consumed 15% alcohol during five months, including the periods of pairing and pregnancy (n=20). The material was obtained at 0, 5, 10, and 61 days. In brain histological sections stained with Nissl stain and using glial fibrillar acidic protein immunohistochemistry, the proportions of unaffected, hypochromic, pyknomorphic, and shadow-like neurons were determined together with the volume of unaffected neurons, oligodendrocyte, astrocyte numbers and neurono-glial index. At day 61 significant reduction in the number of unaffected and slightly changed MDS neurons was found that resulted from increased programmed cell death of neurons and their shrinkage accompanied by a partial compensatory increase in the intensity of neuron-glial interactions due to the increased number of oligodendrocytes. The alcohol addiction behavior of experimental animals was also demonstrated.

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