The Role of the Central Histaminergic System in Behavioral State Control.
2021
Histamine is a small monoamine signaling molecule that plays a role in many peripheral and central physiological processes, including the regulation of wakefulness. The tuberomammillary nucleus is the sole neuronal source of histamine in the brain, and histamine neurons are thought to promote wakefulness and vigilance maintenance - under certain environmental and/or behavioral contexts - through their diffuse innervation of the cortex and other wake-promoting brain circuits. Histamine neurons also contain a number of other putative neurotransmitters, although the functional role of these co-transmitters remains incompletely understood. Within the brain histamine operates through three receptor subtypes that are located on pre- and post-synaptic membranes. Some histamine receptors exhibit constitutive activity, and hence exist in an activated state even in the absence of histamine. Newer medications used to reduce sleepiness in narcolepsy patients in fact enhance histamine signaling by blunting the constitutive activity of these histamine receptors. In this chapter, we provide an overview of the central histamine system with an emphasis on its role in behavioral state regulation and how drugs targeting histamine receptors are used clinically to treat a wide range of sleep-wake disorders.
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