UT Southwestern Identifies Protein Triggering Antidepressant Effect in Brain

UT Southwestern researchers have identified a key protein that helps trigger ketamine’s rapid antidepressant effects in the brain. Although recent studies have shown how quickly ketamine can stabilize severely depressed patients, it is sometimes unlawfully used for its psychedelic effects which could impede memory and other brain functions. The identification of this protein is reportedly a “crucial step” in developing alternatives that could mimic its antidepressant response without the unwanted side effects.

Scientists at the Peter O’Donnell Jr. Brain institute have been working to identify which proteins in the brain ketamine targets to achieve its effects. Dr. Lisa Monteggia, professor of neuroscience at the O’Donnell Brain institute said, “now that we have a target in place, we can study the pathway and develop drugs that safely induce the antidepressant effect.”

The study shows ketamine blocks a protein that is responsible for a range of normal brain functions. The blocking of the protein, which stimulates cellular activity, creates the initial antidepressant reaction while a group of small molecules of ketamine extends the duration of the effect. Although the blocking of this protein receptor creates antidepressant effects in the brain, it is also responsible for many of the drug’s hallucinogenic responses.

While ketamine can distort the senses and impair coordination, studies have shown that it can also stabilize patients within a couple of hours, while other antidepressants often take weeks to produce a response.

Moteggia says that if taken with proper medical care, ketamine may help severely depressed or suicidal patients in need of a quick and effective treatment. “Patients are demanding ketamine, and they are willing to take the risk of potential side effects just to feel better,” she said in a statement. “This demand is overriding all the questions we still have about ketamine. How often can you have an infusion? How long can it last? There are a lot of aspects regarding how ketamine acts that are still unclear.”

Moteggia’s lab is currently conducting two clinical trials with ketamine, including an effort to administer the drug through a nasal spray as opposed to injecting it.

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