Effect of overexpression of the 5-HT7 receptor gene on behavior and brain serotonin system in ASC mice with predisposition to depressive-like behavior

Baraboshkina I.A.¹, Bazovkina D.V.², Ilchibaeva T.V.³, Antonov E.V.⁴, Kulikova E.A.⁵, Naumenko V.S.^6
1ICG SB RAS, irina.10.24@yandex.ru
²ICG SB RAS, daryabazovkina@gmail.com
³ICG SB RAS, rbicehok@mail.ru
⁴ICG SB RAS, a.yegor.v@gmail.com
⁵ICG SB RAS, kulikova.elisa@gmail.com
⁶ICG SB RAS, naumenko2002@gmail.com

Abstract The serotonin (5-HT) system of the brain plays an important role in controlling various behaviors due to the wide variety of serotonin receptors. The 5-HT7 receptor is of great interest because it is involved in the pathogenesis of depressive disorders. Mice of ASC (Antidepressant Sensitive Catalepsy) line with genetic predisposition to depressive-like behavior were obtained in the Laboratory of Behavioral Neurogenomics of ICG SB RAS (Novosibirsk). In this work, the effect of adenoassociated virus (AAV)-mediated overexpression of the 5-HT7 receptor gene in the midbrain on the behavior and brain serotonin system in ASC mice was comprehensively studied. The ASC mice with overexpression of 5-HT7 receptor gene showed the decrease in depressive-like behavior in the forced swim test compared to control group. The introduction of a vector construct with the 5-HT7 receptor gene affected the expression of the gene encoding the 5-HT7 receptor itself, only in the midbrain. The overexpression of 5-HT7 receptor gene in midbrain led to an increase in the serotonin metabolism index in the cortex, hippocampus, and midbrain of mice, without affecting serotonin levels. The results indicate the effect of overexpression of the 5-HT7 receptor gene on the behavior and serotonin system of the brain in ASC mice with a genetic predisposition to depressive-like behavior.