Histamine (HA) is a biogenic amine, providing a number of functional roles throughout the body. HA release triggers inflammatory responses as a protective reaction against foreign pathogens. Released from basophils and mast cells in the periphery, HA causes increased vascular permeability and dilation of blood vessels to allow increased fluid infiltration into tissues which in turn induces swelling. Research designed to test the role of HA in mediating central nervous system (CNS) activity demonstrated that HA immunoreactive brain neurons actively fire action potentials and release HA during the wake phase but are essentially silent during sleep, supporting the hypothesis that increased HA tone is related to levels of wakefulness. Results of experiments investigating the effects of HA in the CNS, either through direct injection of HA or through pharmacological inhibition of its synthesis, show that increases in HA are positively correlated with amounts of wakefulness.

The logic behind sleep deprivation studies is basically sound. The first problem is that sleep is a process that not only occurs in the brain, but is also a process that undoubtedly confers unique benefits to the brain itself. In the parlance familiar to those who are afflicted with a degree in experimental psychology and have thus been subjected to a course in "The Philosophy of Science", the scientific paradigm under which sleep deprivation research is conducted contains some conceptual gaps. The difficulty is as follows: extended continuous wakefulness is an antecedent condition that leads to a predictable, observable outcome: decremented performance. Results from studies conducted to determine the effects of sleep loss on various neurocognitive abilities have proven useful for informing policy, and decision-making in a variety of operational and regulatory environments, and the utilitarian value of such studies for testing work/rest schedules and drug effects remains high.

Narcolepsy is best characterized as a disorder of the regulation of sleep and wakefulness, resulting in a variety of symptoms such as excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations (HH), sleep paralysis, and disturbed nocturnal sleep. This chapter focuses on narcolepsy with cataplexy and narcolepsy without cataplexy. Cataplexy is characterized by a sudden bilateral loss of muscle tone, with preserved consciousness, elicited by emotions. Narcolepsy with cataplexy is diagnosed according to the criteria of the International Classification of Sleep Disorders (ICSD-2). The chapter summarizes the differential diagnoses of EDS and cataplexy. Cataplexy and sleep paralysis are both regarded as expressions of the atonia that physiologically occurs during REM sleep, occurring during wakefulness. Two treatment modalities have proven to be effective: behavioral modification and pharmacological therapy. Pharmacological treatment is supplementary to behavioral advice and should be tailored individually.