Vigilance states, effects

Figure 14.2 Hypocretinergic activity dependent on the states of vigilance. During wakefulness, metabolic, circadian, and behavioral inputs converge on hypocretin neurons, which activate noradrenergic neurons in the locus coeruleus and promote arousal. During non-REM sleep, the activity of hypocretin neurons decreases, but the inhibitory influence of REM-off neurons on REM-on cells is still effective. During REM sleep, hypocretin and REM-off cells are silent, disinhibiting REM-on cells. Reprinted with permission from Sutcliffe de Lecea (2002). (See also Plate 7.)...

Professor Gerhard Zbinden stated that The point at which maximum vigilance is required typically comes when the drug has been on the market for 2-3 years after its sales curve has had time to rise and when effects (good and bad) have had time to show themselves (1). There has been a great deal of controversy over drugs that have been kept on the market despite considerable evidence of worrisome side effects Thalidomide being just one example. 

Low doses of IL-ip or TNF-a have little effects on REM sleep but higher doses generally suppress this state of vigilance. Inhibition of REM sleep might be related to fever. However, the febrile response to exogenously administered cytokines can be selectively suppressed without blocking the sleep-promoting activity (82). 

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