Nav: Home

Ketamine acts fast to treat depression and its effects last -- but how?

June 21, 2018

In contrast to most antidepressant medications, which can take several weeks to reduce depressive symptoms, ketamine -- a commonly used veterinary anesthetic -- can lift a person out of a deep depression within minutes of its administration, and its effects can last several weeks. Researchers have long-wondered how ketamine can both act quickly and be so long-lasting.

Now, researchers led by Mark Rasenick, distinguished professor of physiology and psychiatry in the University of Illinois at Chicago College of Medicine, describe the molecular mechanisms behind ketamine's ability to squash depression and keep it at bay. They report their findings in the journal Molecular Psychiatry.

Two-thirds of participants in clinical studies who did not respond to traditional antidepressants experienced fast and lasting resolution of their depressive symptoms after being given ketamine intravenously, Rasenick explained. The effects of ketamine typically lasted about a week -- much longer than would be expected with ketamine's six-hour half-life in the body.

Rasenick and his colleagues used a cellular model system to investigate how ketamine acted.

In previous research, Rasenick and his colleagues showed that SSRIs -- the most commonly prescribed class of antidepressants, which includes Prozac and Zoloft -- work in the brain by moving molecules called G proteins off of "lipid rafts" on the cell membrane, where the G proteins are held inactive. G proteins produce cyclic AMP, which nerve cells need to signal properly. People with depression, Rasenick found, tend to have a greater proportion of their G proteins packed into these membrane patches, along with dampened brain cell signaling, which may contribute to symptoms of depression, including a feeling of overall numbness.

In the earlier research, when Rasenick exposed rat brain cells to SSRIs, the drug accumulated in the lipid rafts, and G proteins moved out of the rafts. The movement was gradual, over the span of several days, which Rasenick thinks is the reason why SSRIs and most other antidepressants can take a long time to begin working.

In his current research, Rasenick and his colleagues performed a similar experiment with ketamine and noticed that the G proteins left the rafts much faster. G proteins began migrating out of the lipid rafts within 15 minutes. And the long-lasting effects of ketamine may be due to the fact that the G proteins were very slow to move back into the lipid rafts, Rasenick explained.

The finding contradicts the long-held idea that ketamine works solely by blocking a cellular receptor called the NMDA receptor, which sits on the surface of nerve cells and helps transmit signals.

In fact, when the researchers knocked out the NMDA receptor, ketamine still had the same effect on the cells -- quickly moving G proteins out of lipid rafts on the cell membrane.

"When G proteins move out of the lipid rafts, it allows for better communication among brain cells, which is known to help alleviate some of the symptoms of depression," Rasenick said. "Whether they are moved out by traditional antidepressants or ketamine, it doesn't matter, although with ketamine, the G proteins are very slow to move back into the lipid rafts, which would explain the drugs long-term effects on depressive symptoms."

"This further illustrates that the movement of G proteins out of lipid rafts is a true biomarker of the efficacy of antidepressants, regardless of how they work," Rasenick explained. "It confirms that our cell model is a useful tool for showing the effect of potential new antidepressant drug candidates on the movement of G proteins and the possible efficacy of these drugs in treating depression."
-end-
Nathan Wray, Jeffrey Schappi, Harinder Singh and Nicholas Senese of the University of Illinois at Chicago are co-authors on the paper.

This research was supported by VA Merit Award BX00149, and grants R01AT 0009169 and T32 MH067631 from the National Institutes of Health.

University of Illinois at Chicago

Related Depression Articles:

Which comes first: Smartphone dependency or depression?
New research suggests a person's reliance on his or her smartphone predicts greater loneliness and depressive symptoms, as opposed to the other way around.
Depression breakthrough
Major depressive disorder -- referred to colloquially as the 'black dog' -- has been identified as a genetic cause for 20 distinct diseases, providing vital information to help detect and manage high rates of physical illnesses in people diagnosed with depression.
CPAP provides relief from depression
Researchers have found that continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea (OSA) can improve depression symptoms in patients suffering from cardiovascular diseases.
Post-natal depression in dads linked to depression in their teenage daughters
Fathers as well as mothers can experience post-natal depression -- and it is linked to emotional problems for their teenage daughters, new research has found.
Being overweight likely to cause depression, even without health complications
A largescale genomic analysis has found the strongest evidence yet that being overweight causes depression, even in the absence of other health problems.
Don't let depression keep you from exercising
Exercise may be just as crucial to a depression patient's good health as finding an effective antidepressant.
Having an abortion does not lead to depression
Having an abortion does not increase a woman's risk for depression, according to a new University of Maryland School of Public Health-led study of nearly 400,000 women.
Mother's depression might do the same to her child's IQ
Roughly one in 10 women in the United States will experience depression, according to the Centers for Disease Control and Prevention.
Teenage depression linked to father's depression
Adolescents whose fathers have depressive symptoms are more likely to experience symptoms of depression themselves, finds a new Lancet Psychiatry study led by UCL researchers.
Anxiety and depression linked to migraines
In a study of 588 patients who attended an outpatient headache clinic, more frequent migraines were experienced by participants with symptoms of anxiety and depression.
More Depression News and Depression Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.