Interaction of orexinergic and dopaminergic brain stem nuclei neurons in the mechanism of alcoholic dependence, formed in the perinatal period
It is known that a stable deficit of dopamine produced in dopaminergic nuclei of the midbrain and hyperproduction of oligopeptides of the orexin family in the dorsal perifornal region of the caudal hypothalamus, resulting from the morpho-functional interaction of the neurons of the corresponding nuclei of the brainstem, predispose to the development of alcohol dependence. The purpose of this work was to to reveal poorly studied reactive changes in the neurons of the perifornical oroxynergic and paranigral dopaminergic nuclei of the brainstem, as well as changes in the level of orexin A secretion (the main type of orexin) with alcohol dependence formed in the perinatal period. The alcohol dependence of male rats at the age of 61 days was formed by the method of semi-forced alcoholization of females, starting from the 1st day of pregnancy to the 17th day of postnatal development. The methods of light microscopy, quantitative morphometry (counting the number of unchanged / low-modified and shadow neurons in 0.01 mm2 of the area of these nuclei, calculating the area of bodies of small-modified neurons) were used in histological sections, standard statistical processing of the obtained data. The determination of the level of orexin A production was based on a visual assessment of the number of protein granules in the cytoplasm of neurons after their immunocytochemical staining in the perixonal oroxynergic hypothalamic nucleus. As a result of the work, new morphological data were obtained, which clarify the pathogenetic mechanism of the development of alcohol dependence, formed in the perinatal period. The decrease in size and death of a significant part of the peri-ornaxial-nucleus-induced neurons induced by ethanol is less pronounced than in the paranigral dopaminergic nucleus, combined with an increase in the production of orexin A. The alterative changes in the neurons of both nuclei are accompanied by a compensatory effect of macrogol cells on viable neurons that have increased manyfold.