Effects of Chronic Social Stress on the Expression of Neurotransmitter System–Associated Genes in the Hypothalamus of Male Mice

Abstract

Chronic social stress caused by repeated negative experiences in agonistic interactions induces depressive-like behavior in male mice. The aim of this study was to investigate expression changes of genes encoding proteins involved in the metabolism, receptor sensing, and transport of catecholamines, opioids, glutamate, and GABA under the influence of chronic social stress. Hypothalamus samples were analyzed using high-throughput RNA sequencing. It was shown that in the depressed animals, the expression of catecholaminergic genes Adra1b, Adrbk1, Comtd1, Ppp1r1b, Sncb, Sncg, and Th is increased, while the expression of genes Maoa and Maob is reduced. The expression of opioidergic and cannabinoidergic genes Pdyn, Penk, Pomc, Pnoc, Ogfr, and Faah was found to be upregulated, while that of genes Oprk1, Opcml, Ogfrl1, and Cnr1 was downregulated. The expression of glutamatergic genes Grik3, Grik4, Grik5, Grin1, Grm2, and Grm4 was increased, while the expression of Gria3, Grik1, Grik2, Grin2a, Grin3a, Grm5, Grm8, and Gad2 was reduced. The expression of GABAergic genes Gabre, Gabbr2, and Slc6a11 was higher, while the expression of Gabra1, Gabra2, Gabra3, Gabrb2, Gabrb3, Gabrg1, Gabrg2, and Slc6a13 was lower in the depressed animals. The results suggest that the products of genes that interact with other neurotransmitter systems (Th, Gad2, Gabra1, Gabrg2, Grin1, and Pdyn) may be of interest as potential targets for the pharmacotherapy of consequences of chronic social stress.