Sleep-Wake Neurochemistry

Sleep Med Clin. 2022 Jun;17(2):151-160. doi: 10.1016/j.jsmc.2022.03.002.


Behavioral states naturally alternate between wakefulness and the sleep phases rapid eye movement and nonrapid eye movement sleep. Waking and sleep states are complex processes that are elegantly orchestrated by spatially fine-tuned neurochemical changes of neurotransmitters and neuromodulators including glutamate, acetylcholine, γ-aminobutyric acid, norepinephrine, dopamine, serotonin, histamine, hypocretin, melanin concentrating hormone, adenosine, and melatonin. However, as highlighted in this brief overview, no single neurotransmitter or neuromodulator, but rather their complex interactions within organized neuronal ensembles, regulate waking and sleep states. The neurochemical pathways presented here are aimed to provide a conceptual framework for the understanding of the effects of currently used sleep medications.

Keywords: Acetylcholine; Adenosine; Dopamine; GABA; Glutamate; Neuromodulators; Neurotransmitters; Norepinephrine.

Publication types

  • Review

MeSH terms

  • Humans
  • Neurochemistry*
  • Neurotransmitter Agents / physiology
  • Sleep / physiology
  • Sleep Stages / physiology
  • Sleep, REM / physiology
  • Wakefulness / physiology


  • Neurotransmitter Agents