The effects of sleep deprivation on cognitive function may be reversed by treatment with a compound called orexin-A, which occurs naturally in the mammalian brain. The new research was done with rhesus monkeys and may have therapeutic implications for people who suffer from narcolepsy and other sleep disorders, as well as those whose occupations demand a high level of cognitive performance but limit or disrupt normal sleep patterns. “These findings are significant because of their potential applicability,” said Samuel A. Deadwyler, who carried out the study, along with colleagues at Wake Forest University School of Medicine and the University of California at Los Angeles.

The group studied the effects of orexin-A, also called hypocretin-1, on eight adult male rhesus monkeys. The monkeys were given a cognitive test after their normal sleep cycle to determine a baseline performance level. They were then kept awake overnight for 30–36 hours and given the test again. After a 10-day break, the monkeys were again sleep-deprived for 30–36 hours and then given one of two formulations of orexin-A (either intravenous injection or nasal spray) immediately before cognitive testing.

Deadwyler's group found that the cognitive performance of sleep-deprived monkeys was significantly impaired, but treatment with either formulation of orexin-A prevented the decline in cognitive function (J. Neurosci. 27, 14239–14247; 2007). The nasal spray was more effective at improving cognitive function than was intravenous administration. Orexin-A had no effect on cognitive performance in monkeys who were not sleep-deprived. In addition, the researchers carried out noninvasive brain imaging on the monkeys during the cognitive testing. They noted that the brain activity patterns of sleep-deprived monkeys treated with orexin-A were normal, like those of monkeys who had not been sleep-deprived.

Orexin-A is a known sleep-related peptide secreted by specific neurons. Once released, orexin-A can activate many areas of the brain, because its receptors are distributed in various brain regions. Orexin-A had previously been associated with narcolepsy in rats and dogs. This is the first evaluation of orexin-A in primates, and its results indicate that orexin-A is involved with important cognitive processes that are impaired by sleep deprivation. It seems to reactivate specific brain mechanisms rather than simply causing global arousal.

Its specific action and seeming lack of side effects suggest that orexin-A warrants further investigation for applications in treating sleep-related disorders such as narcolepsy. The protein may seem promising but has not yet been tested in humans.