Depression drug may help insomniacs 

By Charlie Fidelman, Vancouver Sun, December 15, 2011, p. B4

Montreal psychiatrist Gabriella Gobbi was testing a new drug on depression in her laboratory when a curious thing happened. The mice fell asleep.

It wasn’t the kind induced by sleeping pills but the deep, restorative slumber of childhood.

Conducted in collaboration with scientists in Italy, the discovery of a novel drug called UCM765 is expected to pave the way for new treatment for sleep disorders, which afflict millions worldwide.

Published in the Journal of Neuroscience, the research on rats and mice found the drug administered under the skin or directly into the brain had two distinct effects on sleep.

Rats fell asleep 60 per cent faster than the control group that did not have the drug, and they slept longer, increasing non-REM sleep, also known as “deep sleep” by 45 per cent, said Gobbi, an associate professor of psychiatry in the Faculty of Medicine at McGill University.

“It was like opening a dark box, a totally unknown world. We found it by serendipity,” said Gobbi, who led a team from the Research Institute of the McGill University Health Centre on a multi-experiment, seven-year study of melatonin receptors.

Gobbi said she often treats people with sleep disorders and depression and the research was driven by her feelings of great sympathy for insomniacs.

Chemists in Italy who developed the drug from the hormone melatonin in 2005 initially had aimed to try to alleviate depression and anxiety.

It also was believed melatonin could alter the circadian rhythm or body clock.

“But its main effect was on sleep,” said Gobbi, whose discovery unveiled the inner workings of melatonin on two receptors in the brain called MT1 and MT2. These are localized in one area of the brain, the reticular thalamic nucleus, which is a “powerhouse of [restorative] sleep,” Gobbi said.

“It was tough because we went against conventional wisdom on melatonin. We thought both receptors would promote sleep and it’s not true; the receptors have opposite roles.”

The team tested the drug on the sleep-wake cycle of rats and mice lacking MT1 or MT2 receptors.

Gobbi’s team induced burst of activity with the drug in MT2 neurons, a key component of deep sleep.

They found that selectively treating one receptor can have therapeutic advantages without the side effects of sleep medication and anti-depressants now marketed for insomnia – for example, drug dependence and cognitive impairment, Gobbi said.