Sleep-promoting effects of cerebrospinal fluid from sleep-deprived goats.

Abstract

In 1913 Legendre and Pieron1 reported that injection of cerebrospinal fluid (CSF) from a sleep-deprived dog into the cisterna magna of a normal animal induced in the recipient for 2-6 hours following the injection. Recipients of fluid from normal dogs remained alert. The hypnotoxic factor was said to be nondialyzable and thermolabile. The Pieron phenomenon was reinvestigated in 1939 by Schnedorf and Ivy,2 who reported positive results in 9 out of 20 trials. The experimental conditions involved severe stress to both donor and recipient animals. Donor animals were deprived of for 7-16 days and the technique of transferring relatively large quantities of CSF from donor to normal recipient without anesthesia undoubtedly involved severe trauma to the experimental animals. For these and other reasons, Schnedorf and Ivy questioned the relevance of the Pieron phenomenon to inormal sleep, although they were conivinced that the phenomenon was real. MVtonnier el al.3' 4 have recenitly reported that electrical stimulationl of ceniters in the thalamus of rabbits causes release of a dialyzable sleep-promoting factor in cerebral venous blood. The role of this substance in the iniitiation of normal is unknown, as is its relation to the nondialyzable material described by Pieron. A humoral factor inducing has also been postulated by Hayashi who reported that CSF obtained during the period of depression following convulsive seizures contains a factor which inhibits convulsions5 and promotes sleep6 when injected intravenitricularly. Hayashi suggested that the active principle might be 4-amino-2-hydroxybutyrate or possibly 4-OH-butyrate. We have now conducted a new investigation of the Pieron phenomenon, taking advantage of new techniques which enable experiments to be carried out under more physiological conditions than were possible iii the past. Crucial to our experiments is all abuittdant supp)ly of CS11' fromn goats which are 1)rovided with ntyloni guide tubes permanently implanted ni. occipital bone above the cistei'aa inagiia.7' 8 CS1i' carn be withdrawni repeatedly from each aniimal at the rate of 0.1 ml/minute foi mainy hours without the use of aniesthesia and without causiing the ainimals any apparent discomfort. For initial trials we prepared five cats with chronically implanted intraventricular cannulas of the Feldberg-Sherwood type.9 The ventricles of these animals were infused slowly (0.1 ml/min) with 1-3 ml of CSF from a inormal goat or from the same goat which had beeni deprived of for 72 hours. Cats which received fluid from sleep-deprived goats fell into a profound or torpor which lasted 12-24 hours; the sleep appeared to be natural in the sense that the cats could be awakened by noise or handling, but reverted to when left tunldisturbed. Sotne animials fell asleep duriiig the infusioin. Similar behavior was not observed when the same cats were infused with control CSF from the same (niotn-sleep-deprived) goats. Tfhese results supported Pieron's observations an-d inidicated that the phen.omenon was not species-specifie. However, laboratory