The search for the hypnogenic center.

1. Electrophysiological and lesion studies have suggested that a number of specific sites in the brainstem and basal forebrain may be involved in the regulation of sleep and waking. In contrast, a study of glucose consumption as measured by the 2-deoxyglucose technique reported a generalized decrease in nonREM sleep compared to waking. The rate of protein synthesis was relatively unchanged in nonREM sleep. 2. Another approach to understanding sleep regulation is to study the mechanism by which hypnotic drugs affect the nervous system. This may be done at both a molecular and neuroanatomic level. Studies with B-carbolines, inverse agonists of benzodiazepines (BZs), indicate that sleep induction by BZs is mediated by binding at the BZ recognition site of the BZ receptor complex. Binding at this site by a long-acting B-carboline parallels the time course of its arousing effects. A study with an enantiomeric BZ indicates that the effects on sleep are stereospecific. It is conceivable that some inverse agonists or enantiomeric benzodiazepines might be developed for clinical use as analeptics. 3. Microinjection of a BZ into the dorsal raphe nucleus acutely increases wakefulness, while administration into the medial preoptic area of the hypothalamus enhances sleep maintenance.