Factors in cerebrospinal fluid from goats that affect sleep and activity in rats

1. Intraventricular infusion in the rat of 0.1 ml. cerebrospinal fluid (c.s.f.) from sleep-deprived goats increases the duration of sleep (measured by e.e.g.) and decreases locomotor activity (measured photo-electrically) for at least 6 hr subsequent to the infusion. Subarachnoid infusions are ineffective.2. C.s.f. from control and sleep-deprived goats was fractionated by ultrafiltration through molecular sieves. The sleep-promoting Factor S is found in the low molecular weight fraction (mol. wt. < 500) of c.s.f. from sleep-deprived but not from control goats.3. The concentration of Factor S in c.s.f. increases progressively during the first 48 hr of sleep deprivation.4. The sleep promoting effects of Factor S cannot be duplicated by serotonin, 4-OH-butyrate, butyrolactone, GABA (gamma-amino butyric acid), glutamic acid or 3',5'-cyclic AMP when these substances are added to control fluids in concentrations up to 10 times greater than those found in normal c.s.f.5. Intraventricular or subarchnoid infusion in the rat of 0.1 ml. proteinfree c.s.f. containing molecules in the mol. wt. range of 500-10,000 at 10-30 x normal concentration causes hyperactivity which persists for several days and nights following the infusion. The excitatory material, probably a peptide, is present in c.s.f. from both control and sleep-deprived goats.6. The properties of Factor S suggest that it may play a role in the normal regulation of sleep and wakefulness.