Ketamine acts as antidepressant by boosting serotonin

Ketamine is a potent anesthetic employed in human and veterinary medicine, and sometimes used illegally as a recreational drug. The drug is also a promising candidate for the fast treatment of depression in patients who do not respond to other medications. New research from the RIKEN Center for Life Science Technologies in Japan demonstrates using PET imaging studies on macaque monkeys that ketamine increases the activity of serotoninergic neurons in the brain areas regulating motivation. The researchers conclude that ketamine's action on serotonin, often dubbed the "feel-good neurotransmitter", may explain its antidepressant action in humans.

The study, published today in the journal Translational Psychiatry demonstrates that Positron Emission Tomography (PET) molecular imaging studies may be useful in the diagnosis of in humans, as well as the development of new antidepressants.

Ketamine has recently been shown to have an antidepressant action with short onset and long-term duration in patients suffering from treatment-resistant major depressive disorder, who do not respond to standard medications such as serotonin reuptake inhibitors, monoamine oxidase inhibitors and tricyclic antidepressants. However, the mechanisms underlying ketamine's action on the depressive brain have remained unclear.

To understand the effects of ketamine on the serotonergic system in the brain, Dr Hajime Yamanaka and Dr Hirotaka Onoe, who has pioneered PET imaging on conscious non-human primates, together with an international team, performed a PET study on rhesus monkeys.

The team performed PET imaging studies on four with two tracer molecules related to serotonin (5-HT) that bind highly selectively to the serotonin 1B receptor 5-HT1B and the serotonin transporter SERT.

From the analysis of the 3 dimensional images generated by the PET scans, the researchers could infer that ketamine induces an increase in the binding of 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. The nucleus accumbens and the ventral pallidum are brain regions associated with motivation and both have been shown to be involved in depression.

In addition, the researchers demonstrate 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.

Taken together, these findings indicate that may act as an antidepressant by increasing the expression of postsynaptic 5-HT1B receptors, and that this process is mediated by the glutamate AMPA receptor.

More information: Yamanaka et al. "A possible mechanism of the nucleus accumbens and ventral pallidum 5-HT1B receptors underlying the antidepressant action of ketamine: a PET study with macaques." Translational Psychiatry, 2013 DOI: DOI: 10.1038/tp.2013.112

add to favorites email to friend print save as pdf

Related Stories

A potential new class of fast-acting antidepressant

Oct 29, 2013

More than 1 in 10 Americans take antidepressants, but these medications can take weeks—and for some patients, months—before they begin to alleviate symptoms. Now, scientists from the University of Chicago have discovered ...

Would an 'anti-ketamine' also treat depression?

Nov 18, 2013

Thirteen years ago, an article in this journal first reported that the anesthetic medication, ketamine, showed evidence of producing rapid antidepressant effects in depressed patients who had not responded to prior treatments. ...

'Special K' could relieve depression

Jun 07, 2012

(Medical Xpress) -- Recreational drug and anaesthetic, ketamine, is being trialled in people with severe depression and is providing almost instant relief from symptoms, offering fresh hope of a quick new ...

Recommended for you

Brains transform remote threats into anxiety

Nov 21, 2014

Modern life can feel defined by low-level anxiety swirling through society. Continual reports about terrorism and war. A struggle to stay on top of family finances and hold onto jobs. An onslaught of news ...

Mental disorders due to permanent stress

Nov 21, 2014

Activated through permanent stress, immune cells will have a damaging effect on and cause changes to the brain. This may result in mental disorders. The effects of permanent stress on the immune system are studied by the ...

Could there be a bright side to depression?

Nov 21, 2014

(Medical Xpress)—A group of researchers studying the roots of depression has developed a test that leads them closer to the idea that depression may actually be an adaptation meant to help people cope with ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.