Ketamine has been known to alleviate depression for a few days up to a week. Now, scientists have discovered how the drug affects brain circuits.

Since it was discovered as a successful anti-depressant, the anesthetic ketamine has already been used to treat thousands of people diagnosed with depression. However, scientists are still baffled as to how the drug really works inside a human's brain.

A Substantial Breakthrough

A study published on April 12 in the online scientific journal Science revealed how researchers were able to closely study how and when Ketamine works inside a functional brain. Mice were used in the experiment, which is a major challenge, according to Dr. Conor Liston, a neuroscientist and psychiatrist at Weill Cornell Medicine in New York and author of the study.

"There's probably no such thing as a depressed mouse,"  said Liston.

To study ketamine's anti-depressant effects on mice, the animals were injected a stress hormone that caused them to act depressed. The depression effects in mice include losing interest in their usual activities such as exploring mazes and eating sugar.

Then, the mice were given doses of ketamine, and by using a special laser microscope, the scientists were able to see the ketamine's effects on the mice's brains. According to Liston, that's when they noticed something surprising.

"Ketamine was actually restoring many of the exact same synapses in their exact same configuration that existed before the animal was exposed to chronic stress," he said. 

Liston and a panel of scientists from Japan and the United States contributed to the experiment.

A Two-Step Process

The experiment proved that ketamine is really effective in treating depression, but scientists are still curious as to how the drug works so fast.

To find out, scientists utilized a technology designed to make living brain cells radiate and glow under a microscope in order to identify groups of brain circuits that light up together.

That's when they found out that in less than six hours that the mice got a dose of ketamine, the brain circuits affected by the stress hormone started working together again. The mice also stopped showing symptoms of depression at the time.

The scientists also discovered that these instantaneous effects had occurred way long before the ketamine was able to restore all the damaged brain synapses.

Because of this, the researchers were able to not only know how ketamine really works but why its effects tend to wear off after a few weeks. 

According to the study, ketamine triggers a two-step process that decreases symptoms of depression. First, the drug somehow persuades the stressed brain circuits to work together again. After that, it also produces a temporary fix that allows the synaptic connections between cells in a circuit to be restored.

Because of the experiment's success, researchers are now leaning to studying how to maintain the brain circuits that ketamine fixed in order to develop a permanent cure to depression.

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