Ketamine reverses depressive-like behavior induced by optogenetic stimulation of glutamatergic neurons in the dorsal hippocampus

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Abstract

The hippocampus is one of the brain structures whose functions and morphology are impaired in depression. The fast-acting antidepressant ketamine reverses these impairments, but the mechanisms of its action are still not fully understood. Optogenetic stimulation of glutamatergic neurons in the CA1 region of the dorsal hippocampus of rats with the preliminary introduction of vectors expressing photosensitive channelrhodopsin led to the manifestation of a sign of depressive-like behavior – an increase in the time of immobility in the tail suspension test, compared to control animals. Immunohistochemical analysis of the expression of the early response protein c-Fos in the CA1 region of the hippocampus confirmed the activation of pyramidal neurons under the influence of light, revealing their involvement in the development of depressive-like behavior. Administration of a subanesthetic dose of ketamine prevented the manifestation of depressive-like behavior trait induced by optogenetic activation of glutamatergic neurons in the CA1 region of the dorsal hippocampus and abolished the increase in c-fos mRNA levels induced by optical stimulation. Thus, we demonstrated for the first time the ability of ketamine to reverse depressive-like behavior trait induced by optogenetic stimulation of the activity of dorsal hippocampal glutamatergic neurons. Overall, the results indicate the important role of dorsal hippocampal glutamatergic neurons in the regulation of psychoemotional behavioral responses and their sensitivity to ketamine administration.

About the authors

U. S. Drozd

Institute of Cytology and Genetics, Siberian Branch of RAS

Email: drozd@bionet.nsc.ru
Novosibirsk, Russia

E. V. Sukhareva

Institute of Cytology and Genetics, Siberian Branch of RAS

Email: drozd@bionet.nsc.ru
Novosibirsk, Russia

V. V. Bulygina

Institute of Cytology and Genetics, Siberian Branch of RAS

Email: drozd@bionet.nsc.ru
Novosibirsk, Russia

T. S. Kalinina

Institute of Cytology and Genetics, Siberian Branch of RAS; Novosibirsk State University

Email: drozd@bionet.nsc.ru
Novosibirsk, Russia; Novosibirsk, Russia

N. N. Dygalo

Institute of Cytology and Genetics, Siberian Branch of RAS; Novosibirsk State University

Email: drozd@bionet.nsc.ru
Novosibirsk, Russia; Novosibirsk, Russia

D. A. Lanshakov

Institute of Cytology and Genetics, Siberian Branch of RAS; Novosibirsk State University

Author for correspondence.
Email: lanshakov@bionet.nsc.ru
Novosibirsk, Russia; Novosibirsk, Russia

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