Histamine Plays an Important Role in Promoting and Stabilizing Wakefulness^1-3

In the brain, hypocretin (orexin) and histamine neurons play complementary roles⁴

Hypocretin and histamine promote wakefulness by activating the cortex and wake-promoting neurons^2,3
Hypocretin and histamine help stabilize wakefulness by inhibiting REM sleep–promoting neurons and non-REM sleep–promoting neurons^1-3

References

Scammell TE, Jackson AC, Franks NP, Wisden W, Dauvilliers Y. Histamine: neural circuits and new medications. Sleep. 2019;42(1). doi:10.1093/sleep/zsy183
Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron. 2017;93(4):747-765.
Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88(3):1183-1241.
Anaclet C, Parmentier R, Ouk K, et al. Orexin/hypocretin and histamine: distinct roles in the control of wakefulness demonstrated using knock-out mouse models. J Neurosci. 2009;29(46):14423-14438.