Table 2.

Sleep-Related Neurotransmitters

Neurotransmitter	Site of origination	Wake promoting or sleep promoting	Relative activity	Comments
Adenosine	Extracellular space	Sleep	NREM>REM>>Wake	Metabolized during NREM sleep
GABA	VLPO	Sleep	NREM>>REM>Wake	Main NREM neurotransmitter
Melatonin	Pineal gland	Sleep	NREM>REM>Wake	Converted from serotonin in the pineal gland
Glutamate	Cortex	Wake	Wake = REM>NREM	Main CNS excitatory neurotransmitter
Dopamine	Substantia nigra	Wake	Wake = REM>NREM	Neither wake nor sleep promoting; active in dreams
Orexin (hypocretin)	Hypothalamus	Wake	Wake>>REM = NREM	Regulates REM-on and REM-off
Acetylcholine	Basal forebrain	Wake	Wake> = REM>>NREM	Most active wake, but also REM sleep (REM-on)
Norepinephrine	Locus ceruleus	Wake	Wake>NREM>>REM	Suppresses REM (REM-off)
Serotonin	Dorsal raphe nucleus	Wake	Wake>NREM>>REM	Suppresses REM (REM-off)
Histamine	Tuberomamillary nucleus	Wake	Wake>>NREM>REM

>> connotes a greater difference than >

NREM, non-rapid eye movement; REM, non-rapid eye movement; VLPO, ventrolateral preoptic; CNS, central nervous system.