How ketamine keeps depression at bay

 Washington D.C. [USA]: A recent research has found how ketamine, unlike most antidepressant medications, can lift a person out of a deep depression within minutes of its administration.

Researchers, led by Mark Rasenick, University of Illinois at Chicago College of Medicine, describe the molecular mechanisms behind ketamine's ability to squash depression and keep it at bay.

"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 his current research, Rasenick and his colleagues performed an 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."

The study appears in the journal Molecular Psychiatry.