Since the early experiments conducted by Legendre and Perone, a number of substances found in the blood, urine, and cerebrospinal fluid have been referred to as “sleep factors”.  Specific REM sleep factors accumulates in the brain during REM sleep and may regulate REM sleep, based on the finding that the cerebrospinal fluid from REM sleep deprived cats induced REM sleep when injected into the brain of other cats.  Since then, this same phenomenon has been shown to occur in rats.  This effect seems to be dose dependent, with a higher dose producing higher REM sleep episode numbers and a greater increase in REM sleep episodes.  Presently, scientists do not know what chemicals make up this mystery factor.  However, they are certain that VIP, CCK, and CLIP, all brain peptides that enhance REM sleep, are not present.

   Average glucose utilization in the whole brain is not changed in sleep deprived rats.  However, decreased utilization is found in specific brain areas including the hypothalamus, thalamus, temporal lobe, and limbic system, all areas involved in regulating body temperature, sleep functions, and endocrine regulation. In humans, positron emission tomography indicates decreased glucosemetabolism in the thalamus, basal ganglia, white matter, and cerebellum.