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In 1913 Legendre and Pieron' reported that injection of cerebrospinal fluid (CSF) from a sleep-deprived dog into the cisterna magna of a normal animal induced sleep 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 sleep 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 normal sleep, although they were convinced that the phenomenon was real.Monnier et al.3' 4 have recently reported that electrical stimulation of "sleep centers" in the thalamus of rabbits causes release of a dialyzable sleep-promoting factor in cerebral venous blood. The role of this substance in the initiation of normal sleep is unknown, as is its relation to the nondialyzable material described by Pieron. A humoral factor inducing sleep 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 intraventricularly. 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 in the past. Crucial to our experiments is an abundant supply of CSF from goats which are provided with nylon guide tubes permanently implanted in occipital bone above the cisterna magna.7 8 CSF can be withdrawn repeatedly from each animal at the rate of 0.1 ml/minlute for many hours without the use of anesthesia and without causing the animals any apparent discomfort.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 normal goat or from the same goat which had been deprived of sleep for 72 hours. Cats which received fluid from sleep-deprived goats fell into a profound sleep 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 sleep when left undisturbed. Some animals fell asleep during the infusion. Similar behavior was not observed when the same cats were infused with control CSF from the same (non-sleep-deprived) goats. These results supported Pieron's observations and indicated that the phenomenon was not specie...

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A simple method is described for obtaining repeated measurements of body temperature in young mice with minimal error introduced through stress. Temperatures are measured by an external thermocouple attached to the thorax in the region of the heart. A sling around the animal's thorax provides insulation for the thermocouple from surrounding air and mild restraint of the animal during measurement. Comparison with temperatures obtained in other locations indicates that external thoracic temperature as described gives a reliable estimate of true body temperature in mice up to 21 days old. Typical results with normal mice aged 1 day to 6 wk postpartum are included, together with a brief discussion of the technique's applicability.

It was recently shown that morphine, like 5-hydroxytryptamine (5-HT), produces hypothermia in rats, but hyperthermia in cats, when acting on the anterior hypothalamus (Lotti, Lomax & George, 1965; Banerjee, Feldberg & Lotti, 1968). Because morphine depletes the monoamines of the brain the possibility has been discussed that 5-HT may be the mediator of its temperature effects in these species. In the present experiments morphine was injected into the cerebral ventricles of rabbits to see if in this species, too, its effect on temperature resembles that of 5-HT similarly applied.In the course of the experiments, an effect of morphine was obtained which so far seems to have been observed with this alkaloid in rats only (Reynolds & Randall, 1957)-that is, catalepsy. It developed not only when the morphine was given by the intraventricular route but also following its injection into the cisterna magna. METHODSNew Zealand white or Dutch rabbits of both sexes weighing 1.7-3 kg were used. A Collison cannula was aseptically implanted under pentobarbitone sodium anaesthesia into the left lateral cerebral ventricle. The point of insertion was 7 mm lateral to the midpoint of the sagittal suture as described by Hasselblatt & Sproull (1961). An interval of at least 3 days was allowed between implantation of the cannula and the injection of drugs. They were injected in a volume of 0.1 ml. followed by 0.05 ml. of 0.9% NaCl solution.For injections into the cisterna magna the rabbit was restrained by hand, the neck was flexed and a 23 gauge needle with stilette was pushed through the skin and muscle in the midline just posterior to the lower margin of the occipital bone until the tip of the needle was felt to penetrate the dura. If the tip had entered the cisterna, clear cerebrospinal fluid (c.s.f.) welled up in the hub of the needle when the stilette was removed. A 1 ml. glass syringe filled with either 0.9% NaCl or the morphine solution was then attached to the needle and a volume of 0.1 ml. fluid was allowed to flow in by gravity. If no c.s.f. appeared in the needle hub or if the fluid was tinged with blood, no injections were made. Little discomfort seemed to be caused either by insertion of the needle or by the injection, for the rabbit made no attempt to struggle.In order to see which areas of the brain are reached by solutions injected in this way, 0.1 ml. of a 0.2% solution of bromophenol blue, prepared as described by Feldberg & Fleischhauer (1960a), was injected into the cisterna magna of unanaesthetized rabbits. Within a few minutes this produced vigorous scratching movements which result from an action on structures near the dorso-lateral surface of the upper cervical cord, because bromophenol blue applied to this region is known to