Characterized by restlessness, irritability, persistent sadness, and fatigue, major depression is a serious mental illness. It’s also common, affecting approximately 280 million people around the world. Fortunately, ketamine has emerged as a rapid-onset option for patients with treatment-resistant depression.
As a dissociative anesthetic, ketamine can induce a state of sedation, along with certain hallucinogenic effects. It also offers powerful depression relief, particularly among patients expressing suicidality. But while experts are optimistic about ketamine’s role in depression intervention, the actual mechanism behind ketamine’s function as a rapid antidepressant is still poorly understood by the scientific community. Thus, a team of brain and mental health specialists in China and the U.S. sought to explore those mechanics. In their study, published in the journal Science, the group administered ketamine to depressed mouse models to observe ketamine’s effects on the brain. The results could drive precision ketamine treatment in the future. Read on to find out more about the study.
Ketamine Targets Specific Brain Receptor for Rapid Antidepressant Effects
As mentioned above, researchers have explored ketamine as an option to help people overcome depression symptoms quickly — often much more quickly than with traditional medications. However, the precise mechanism is unknown. There has been some prior research into the topic, suggesting that ketamine acts as a noncompetitive antagonist of a receptor known as the N-methyl-D-aspartate (NMDA) receptor. This receptor is a glutamate receptor, working to stimulate nerve cells and contributing to everyday neurological function. The question was: How does ketamine stimulate the NMDA receptor, and how might that knowledge be used in future treatment for depression?
Explore the Link Between Ketamine and the NMDA Receptor
To determine the direct link between ketamine and the NMDA receptor, the research team conducted experiments using mice induced to express certain depressive symptoms. The team administered ketamine to the mouse models via injection; other mice, serving as controls, received saline instead of ketamine injections.
After injecting the mice, the researchers measured synaptic currents in the cells with NMDA receptors in the hippocampus. Ketamine did not block NMDA receptor currents associated with neurons in the hippocampus. Afterwards, the team studied the rodents’ brains slice by slice using in vitro electrophysiology. Ultimately, the researchers found that injecting the mice with ketamine effectively blocked NMDA receptor currents in the lateral habenula, a central structure of the brain that is often associated with the pathology of psychiatric disorders including major depression. This function revealed what the team needed to know, suggesting that these neural structures are key to ketamine’s unique blockade effect.
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This research could have lasting impacts on tailoring ketamine for targeted use in individuals with depression. The research team concludes: “By increasing the intrinsic activity of hippocampal neurons or decreasing the activity of lateral habenula neurons, the sensitivity of their NMDA receptor responses to ketamine blockade could be swapped.” Additionally, the study could contribute to making ketamine treatments more accessible, allowing patients to benefit from the unique mechanism of this depression treatment without having to receive injections in a clinical setting.
To explore the effects of antidepressants, Scantox Neuro can treat mice and rats via different routes and evaluate behavioral differences by applying anxiety and depression tests. Furthermore, drug effects can be evaluated by biochemical and histological analysis methods.
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