Abstract

Chronic social stress leads to the development of mixed anxious/depressive disorders in male mice, similar to those in humans. Changes in the functioning of many neurotransmitter systems have been shown to occur in the brains of depressed animals. The aim of the present work was to study the expression genes encoding proteins involved in the metabolism, transport, and reception of serotonin, catecholamines, glutamate, and GABA in the ventral tegmental area of the brain – an area playing an important role in regulating motivations and emotions and involved in the mechanisms underlying the development of affective disorders. Mixed anxious/depressive disorder in animals was formed by chronic social stress for 20 days. Samples of ventral tegmental area were sequenced at Genoanalytica ( http://genoanalytica.ru /, Moscow, Russia). Expression of the serotoninergic genes Tph2, Maob, Htr4, Htr1a, and Slc6a4 was increased in depressed animals, while expression of the Htr3a gene was decreased. The expression of the dopaminergic genes Th, Ddc, Slc6a3, Slc18a2, Drd2, and Maob was increased and the expression of the noradrenergic genes Dbh, Slc6a2, Adra2c, and Adra2a was decreased. Expression of the GABAergic genes Gabra1, Gabra2, Gabrg2, Gabrg1, Gabrq, Gad1, and Gad2 and the glutamatergic genes Gria1, Gria2, Grik2, Grm2, Grm5, and Slc17a8b was greater in depressed animals than controls. Formation of mixed anxious/depressive disorder in response to chronic social stress in mice led to increases in the expression of genes encoding proteins involved in the operation of the serotoninergic, dopaminergic, glutamatergic, and GABAergic systems, while expression of genes responsible for adrenergic reception decreased. It is suggested that a key role in the synchronous changes in the expression of genes for different neurotransmitter systems may be played by the Drd2 and Htr3a genes.

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