INFLUENCES OF RELATED SUBSTANCES OF TRICARBOXYLIC ACID CYCLE UPON PARADOXICAL SLEEP

Abstract

Investigations into the influences of precursors, members, and inhibitors of the citric acid cycle upon the sleep patterns were carried out in the rabbit with chronically implanted electrodes. The effects of these substances were compared before and after the pre-collicular transection.EMGs were recorded from m. trapezius-pars cervicalis and m. scutuloauricularis superior, EEGs from the frontal cortex, olfactory bulb, and dorsal hippocampus. Changes of the duration and latency of the firstly appeared signs of the paradoxical sleep (PS) after injection of such substances into the aural vein, were adopted as criteria of the facilitatory or inhibitory effects of the substances upon the PS. The results are as follows:A. In the decerebrate animal: 1) the latency of 31-190sec. and the duration of 50-470sec. are characteristic of the PS evoked by administering glucose-(10-30mg), and lactic acid (1.0-2.0mg), and pyruvic acid (1.0-2.0mg). 2) administration of 0.8-3.0mg of the members of the tricarboxylic acid cycle evoked the PS with latency of 20-270sec. and duration of 30-470sec. 3) spontaneous paradoxical sleep phase was not observed for more than 4 hours after the administration of fluoroacetate (0, 4-1.0mg); for 2 hours or more after the administration of malonic acid (1.0-2.0mg). Even if by co-administration of the inhibitors together with the precursors or the members of tricarboxylic acid cycle in gram equivalent, the PS was blocked. 4) after administering the short chain fatty acids (from C2 to C6; 0.6-1.2mg), acetoacetate (1.0-2.0mg) or acetone (0.8-1.2mg) the PS appeared with latency of 21-345sec. and duration of 20-487sec. 5) injection of DPNH (0.7-0.9mg) exercised a marked facilitatory effect upon the evocation of PS with 20-75 seconds latency and 180-960 seconds duration, whereas DPN, TPN or TPNH had no marked facilitating effect, but not produced inhibitory effect. 6) 2, 4-dinitrophenol (0.5-1.5mg) and 2, 3-dimercaptopropanol (0.7-1.0mg) produced neither facilitatory nor inhibitory effect.B. In the intact rabbit, after administration of such precursors and members of the tricarboxylic acid cycle and DPNH, the PS was evoked as in the precollicular animal. However, the latency was longer than in the pre-collicular animal, while the duration was shorter. The PS threshold to direct electrical. stimulation of the septum or the hypothalamus decreased by 40-70 per cent of the control after injection of these substances. No appreciable change in the total amount of PS episodes was revealed following administration of 2, 4-dinitrophenol (0.5-1.5mg) or 2, 3-dimercaptopropanol (0.7-1.0mg), but an increased amount of total PS for 4 hours after administration of the precursors and the members of tricarboxylic acid cycle, and such coenzyme in respiratory chain as DPNH was observed. On the other hand, the appearance of PS was blocked by administration of fluoroacetate (0.4-1.0 mg) or malonic acid (1.0-2.0mg) just as in the case of the supracollicular transected rabbit.C. In the control experiments of the intact animal, 0.2-0.3ml. of distilled water or physiological saline was administered and the PS appeared after the injection with the lapse of 22min. 30sec. to 58min. 50sec. except for one case with 19min. 10sec. After the transection it took 8min. to 30min. before the PS appearance.