Neurotransmitter reverses sleep deprivation

By Karla Gale

NEW YORK (Reuters Health) - Administration of orexin-A, a naturally occurring brain neurotransmitter, counteracts the intellectual deficits and altered brain metabolism induced by sleep deprivation in monkeys, new research findings show.

Orexin-A was tested because of its know specific brain activity in controlling sleep processes in mammals, lead author Dr. Sam A. Deadwyler told Reuters Health.

Orexin-A is released by neurons in the brain, the scientists explain in the Journal of Neuroscience, and orexin-A receptors are located on neurons in many brain regions affected by sleep and sleep deprivation.

Deadwyler, a neurobiologist at Wake Forest University in Winston-Salem, North Carolina, and his team worked with eight monkeys trained to perform an intellectual task to test short-term memory.

The effect of orexin-A on the animals' performance was analyzed after a normal 12-hour sleep cycle and after being kept awake for 30 to 36 continuous hours. Brain metabolism was evaluated by F18-fluorodeoxyglucose PET scanning.

When the monkeys were alert, orexin-A did not improve test performance. In fact, at the highest concentration of orexin-A, intellectual functioning worsened.

However, when the monkeys were deprived of sleep, a low- or high-dose of orexin-A significantly improved the animals' test performance.

It was even more potent when it was administered through the nose. Cognitive performance was restored to normal alert levels, and nasal orexin-A improved performance on more difficult tests.

During sleep deprivation, glucose metabolism in various portions of the brain was reduced, while a compensatory increase was observed in another portion. Similar to the effects seen on intellectual function, orexin-A reversed these changes and nasal administration achieved a greater effect.

These study findings provide "strong evidence" that nasal administration of orexin-A can correct the intellectual deficits caused by sleep deprivation, the scientists conclude.

However, before this agent can be offered to long-haul truckers or military personnel, for whom sleep is often limited, the effect of orexin-like agents on other brain processes that are not related to loss of sleep need to be evaluated, Deadwyler said. "Our study did show minor impairment of normal performance with relatively high systemic doses of orexin."

SOURCE: Journal of Neuroscience, December 26, 2007.