Ketamine Reverses Depressive-Like Behavior Induced by Optogenetic Stimulation of Glutamatergic Neurons in the Dorsal Hippocampus
U. S. Drozd
Нейрохимия / Neurochemical Journal 2025 DOI: 10.7868/s3034556125010065 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Optogenetic stimulation Ketamine |
| Dose | subanesthetic dose |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine reversed depressive-like behavior induced by optogenetic activation of glutamatergic neurons in the CA1 region of the dorsal hippocampus in rats. |
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |