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Scientists Discover How Ketamine Treats Depression

Update Date: Jan 07, 2014 06:31 PM EST

Ketamine treats depression by boosting serotonin, according to a new study. The anesthetic, which is sometimes used illegally as a recreational drug, is a promising candidate for the treatment of depression in patients who cannot be helped by other drugs.

New research on macaque monkeys reveals that the drug increases the activity of serotoninergic neurons in the brain areas regulating motivation. Scientists said the findings suggest that ketamine's action on serotonin may explain how it relieves depression in people.

While previous studies found that ketamine has an antidepressant action with short onset and long-term duration in patients suffering from treatment-resistant major depressive disorder, the mechanisms underlying ketamin's action for relieving depression have been unclear.

After performing PET scans on rhesus monkeys, researchers found that ketamine triggers an increase in the binding of serotonin to its receptor 5-HT1B in the nucleus accumbens and the ventral pallidum, but a decrease in binding to its transporter SERT in these brain regions. Previous studies have linked both brain regions, the nucleus accumbens and the ventral pallidum, to motivation and depression.

Further experiments revealed that treatment with NBQX, a drug known to block the anti-depressive effect of ketamine in rodents by selectively blocking the glutamate AMPA receptor, cancels the action of ketamine on 5-HT1B but not on SERT binding.

Researchers explained that both these findings suggest that ketamine may act as an antidepressant by boosting the expression of postsynaptic 5-HT1B receptors, which is mediated by the glutamate AMPA receptor.

The fidnigns are published in the journal Translational Psychiatry.

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