Picrotoxin-Barbiturates Antagonism in Decorticated Animals *

The problem of the sleep-waking mechanism may be approached by a study of the toxins known to induce the states of sleep or awakening, and by investigation, particularly, of the antagonism of sleepand wake-inducing drugs. A primary consideration is the localization of the effects of these agents. The studies of Maloney, Fitch, and Tatum have shown that picrotoxin is very effective in awakening an animal from barbiturate sleep. This antagonistic action between picrotoxin and barbiturates proved to be of clinical value also. The series of experiments here presented was designed to ascertain whether the presence of a functioning cerebral cortex is essential for the awakening action of picrotoxin. Koppanyi suspected that the cortex participates in this mechanism. Together with his co-workers, he observed that the excitability of the motor cortex in dogs, abolished after intravenous administration of pentobarbital, was restored upon intravenous injection of picrotoxin. Whereas the convulsive effect of this toxin may still be observed after destruction of the hemispheres (Grunwald, Morita) or section below the optic thalami (Pollock and Holmes), direct application to the cerebral motor cortex, according to Sollman, produces some stimulation. For the experiments reported in this communication rats were chosen because in them, as is well known, the cortex is readily extirpated by suction. Accordingly, the cerebral hemispheres were exposed under ether anesthesia and, by means of glass tubes connected to a suction pump, the cortex was sucked out. First, tubes with a diameter of 3 mm. were employed and then tubes ending in a capillary for the removal of remaining particles of the cortex. Careful attention to the control of hemorrhage is important. Within