Dorsal Raphe Nucleus Serotonergic Neuron Activity is Necessary for the Manifestation of the Antidepressant Effect of Ketamine.

Abstract—The mechanisms of the ketamine antidepressant effects observed in humans and laboratory animals are not fully understood. To further clarify the role of brain serotonergic (5-HT) activity in the action of antidepressant drugs, optogenetic inhibition of 5-HT neurons in the rat dorsal raphe nucleus (DRN) was applied. In control animals, a subanesthetic dose of ketamine alleviated their depressive-like behavior in the tail suspension test. Inhibition of 5-HT neurons abolished the drug effect and moreover, a sedative response to ketamine was found under these conditions. Furthermore, optogenetic suppression of the activity of 5-HT neurons prevented the increase in c-Fos expression induced by ketamine both in light-sensitive neurons and in other DRN neurons. The data emphasize the key role of 5-HT neuron activity in the rapid ketamine antidepressant effect. [ABSTRACT FROM AUTHOR]