Serotonin 5‐HT <sub>7</sub> receptor overexpression in the raphe nuclei area produces antidepressive effect and affects brain serotonin system in male mice
A. Ya. Rodnyy, Е. М. Кондаурова, Д. В. Базовкина, Elisabeth A. Kulikova, T. V. Ilchibaeva, A. I. Kovetskaya, I. Baraboshkina, E. Yu. Bazhenova, Н. К. Попова, В. С. Науменко
Abstract
Abstract Heterodimerization between 5‐HT 7 and 5‐HT 1A receptors seems to play an important role in the mechanism of depression and antidepressant drug action. It was suggested that the shift of the ratio between 5‐HT 1A /5‐HT 7 hetero‐ and 5‐HT 1A /5‐HT 1A homodimers in presynaptic neurons toward 5‐HT 1A /5‐HT 1A homodimers is one of the reasons of depression. Consequently, the artificial elevation of 5‐HT 7 receptor number in presynaptic terminals might restore physiological homo‐/heterodimer ratio resulting in antidepressive effect. Here we showed that adeno‐associated virus (AAV)‐based 5‐HT 7 receptor overexpression in the midbrain raphe nuclei area produced antidepressive effect in male mice of both C57Bl/6J and genetically predisposed to depressive‐like behavior ASC (antidepressant sensitive cataleptics) strains. These changes were accompanied by the elevation of 5‐HT 7 receptor mRNA level in the frontal cortex of C57Bl/6J and its reduction in the hippocampus of ASC mice. The presence of engineered 5‐HT 7 receptor in the midbrain of both mouse strains was further demonstrated. Importantly that 5‐HT 7 receptor overexpression resulted in the reduction of 5‐HT 1A receptor level in the membrane protein fraction from the midbrain samples of C57Bl/6J, but not ASC, mice. 5‐HT 7 receptor overexpression caused an increase of 5‐HIAA/5‐HT ratio in the midbrain and the frontal cortex of C57Bl/6J and in all investigated brain structures of ASC mice. Thus, 5‐HT 7 receptor overexpression in the raphe nuclei area affects brain 5‐HT system and causes antidepressive effect both in C57Bl/6J and in “depressive” ASC male mice. Obtained results indicate the involvement of 5‐HT 7 receptor in the mechanisms underlying depressive behavior.