NEUROPHARMACOLOGICAL STUDIES ON THE MECHANISMS OF PARADOXICAL SLEEP IN THE RABBIT

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Abstract
Employing rabbits with bipolar electrodes chronically implanted in several parts of the brain, the effects of some hypnotics, sedatives or tranquillizers upon paradoxical sleep were investigated through observations on the distribution of spontaneous PS episodes and through measurements of the induced PS threshold. PS ceased to appear and the PS threshold was elevated by the administration of 80mg/kg body weight of bromvaleryl urea, 0.1g/kg body weight of ethinamate, 12mg/kg body weight of pentobarbital sodium or 2mg/mg body weight of morphine sulphate. On the other hand, after the administration of 40mg/kg body weight of 2-methyl-3-o-tolyl-quinazolone (MTQ), PS threshold fell while the EEG arousal threshold rose. After the administration of 1.5mg/kg body weight of chlorpromazine 6mg/kg body weight of amitriptyline or 120mg/kg body weight of meprobamate, no change was observed on the EEG arousal threshold but the PS threshold markedly raised its level. After the administration of 2mg/kg body weight of chlordiazepoxide or 0.2 mg/kg body weight of diazepam, no effect was observed on the EEG arousal threshold while PS threshold decreased its level. The recruiting response to stimulation of the centre median nucleus of the thalamus recorded from the frontal cortex was enhanced after 0.1g/kg body weight of ethinamate and after 40mg/kg body weight of MTQ. On the other hand, 1.5mg/kg body weight of chlorpromazine and 3mg/kg body weight of chlordiazepoxide had almost no effect upon the response. The effects of pentobarbital, MTQ, chlorpromazine and chlordiazepoxide upon EEG activity in the pontine reticular formation, which was assumed to be the PS generating center by JOUVET, were investigated and it was found that pentobarbital sodium markedly depressed its activity and chlorpromazine depressed it slightly, but MTQ and chlordiazepoxide produced no change. Therefore, it may be reasonable to assume that it is not by direct action on the pontine reticular formation that these two latter drugs have a facilitatingeffect on PS. In conclusion it was elucidated that the PS generating system was independent of the diffuse activating system or the recruiting system. Furthermore it was suggested that these drugs which had an inhibitory effect in the tricarboxylic acid cycle simultaneously showed a blocking effect upon the PS appearance.