Science 329, 959–964 (2010)

Patients taking traditional antidepressants have to wait several weeks for the drugs to kick in. However, a few severely depressed patients taking ketamine, an anaesthetic and recreational drug, have shown improvement within hours. How does it act so quickly?

Ronald Duman and his team at Yale University in New Haven, Connecticut, show that the ketamine affects a brain signalling pathway called mTOR. Ketamine rapidly activated this pathway in the prefrontal cortex of healthy rats, resulting in the formation of more connections between neurons. Treated rats also showed improved performance in three behavioural tests that model depression. These responses were all lost when the scientists blocked the mTOR pathway biochemically.