Аннотация:
The study shows that the orexin system is involved in the stabilization of the cellular genome during chronic alcoholization in rats. To determine the genotoxic damage to peripheral blood cells, a micronucleus test was used. Chronic administration of ethanol led to destabilization of the genome of erythrocytes and peripheral blood lymphocytes. Intranasal administration of orexin A for 7 days (1 mg/ml, 20 µl) in chronically alcoholized rats did not cause changes in the indicators of genome destabilization. In the group of alcoholized animals treated with the selective orexin type 1 receptor antagonist (OX1R) SB-408124 (1 mg/ml, 20 µl, intranasally, for 7 days), a significant decrease in the number of micronuclei in erythrocytes and peripheral blood lymphocytes was observed compared with the group of animals, receiving only ethanol. In the course of studying the effect of the OX1R antagonist SB-408124 on the conditioned ethanol place preference reaction (CPP), it was shown that intranasal administration of the OX1R antagonist SB-408124 blocks the expression of CPP and the reinstatement of alcohol CPP after its extinction in alcoholized rats. Taken together, the obtained data indicate the directed action of the orexin OX1R receptor antagonist SB-408124 in organizing the processes of genome stabilization in chronically alcoholic rats and in reducing the addictive properties of ethanol in them. The prospect of creating pharmacological agents based on orexin receptor antagonists that affect the processes of regulation of genome stability and aimed at the treatment of pathological conditions, such as addictive disorders, is noted.
Ключевые слова:
orexin, orexin receptors, lymphocytes with micronuclei, chronic alcoholization, peripheral blood mononuclear cells, stress exposure.