1.Rats were conditioned by using sound as a conditioned simulus, and tetrabanazine as an unconditioned stimulus, andsponraneous locomotor activity as parameter of behavior. 2.A difinite period of motionlessness in rats appeared on presentation of a conditioned stimuluts alone, after a definite number of conditioning trials were repeated. 3.Pretreatment with imipramine made the conditioned motionlessness imperfect. 4.From these findings, this conditioned motionlessness was considered as an appropriate animal model of human depression. 5.Biochemical analyses of brain samples indicated that this motionlessness was due to an excess in functional activity serotonin.

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In order to examine the underlying brain mechanism of depression, we designed to investingate the changes in brain monoamines of the "depression model animal". For this purpose, we used female rats which had a regular cycle of spontaneous running activity corresponding to the estrus cycle.Having confirmed the regular cyclic activity, animals were repeatedly exposed to stress in terms of forced running. We thus succeeded in producing chronically inactive animals in which the estrus cycle had been abolished even after the animals recovered from physical exhaustion. This stress-induced, long lasting, inactive state, accompanied by the abolition of hormone dependent cyclic behavior, was suppused to be a "depression analogue". Rat's brains were examined by the fluorescence histochemical method. The most significant findings common to the "depression model rats" were as follows : 1.Fluorescence intensity in nerve cells of the ascending NA systems(A1.A2.A5.A6.A7.)was markedly increased. 2.Fluorescence intensity in cell bodies and nerve terminals of the tubero-infundibular DA systems was decreased. Since these findings were also found in the rats immediately after the stress and were restored to control levels in the "recovery rat", it is conceivable that the changes in brain monoamines induced by stress remain unrestored due to a certain mechanism for long time in "depression model animals".

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Various kinds of experimental ulcers have been used as a disease model of human peptic ulcer in the field of psychosomatic medicine for the purpose of investigating the significance of emotional stimuli to the occurrence and healing of ulcer. Several techniques to produce the gastric lesions in rats and mice were introduced. Acute gastric lesions were utillized to elucidate the relationship between susceptibility to ulcers and noxious emotional stimuli such as immobilization, communicated emotional stimuli and psychologically devised immobilization as well as an individual basic emotional trait. Repeated immobilization could produxe the deep ulceration with changes especially in the fore-stomac in the rats. Communicated emotional stimuli and psychological immobilization developed gastric lesions successfully in mice, though no physical stressors were employed here. Chronic experimental ulcers are applied to investigate the influence of the emotional stimuli on the healing process of ulcers. Acetic acid ulcers were used here as a chronic ulcer model, but none of these emotional stimuli could give any influence upon this process exept the basic emotional trait of being hypoactive in open field test.

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Experimental ulcers induced by various kinds of stress have been used as a model for the gastric and duodenal ulcers which are the typical ones in psychosomatic diseases. The restrained water immersion method is the most popular. We have used this method in rats, monkeys and dogs and observed the successive gastric mucosal changes using a gastrofiberscope without sacrificing the animals. The gastrofibenscope idebtified what kinds of changes occurred, where they began and how long they lasted. We could also estimate the effects of some psychotropic drugs in these same animals. We presented actual methos and results, and discussed our findings. Naturally occurring human gastric ulcers are somewhat different from experimental ulcers in animals, especiallu the chronic ones. It is difficult to induce exparimental chronic ulcers in animals which will resemble those found in man. Using the gastrofiberscope we injected 8% acetic acid into the gastric mucosa of dogs. With this method, we could induce ulcers which require lengthy healing periods. These ulcers, however, are essentially different from those found in man. We pointed out limits of experimental ulcers and considered the various involved.

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This article attempts to summarize certain simple applications of principles of lerning and behavior theory that are bilieved to be relevant to psychosomatic medicine. These is a simple experimental design that isolates the psychological effects from the effects of the physical stimulus. The triadic procedure consists of exposing two or more animals to exactly the same physical stressor while each subject is in a different psychological condition. It provides a direct test of hypothesis that it is not physical stressor itself but psychological factors, that cause the psychosomatic diseases. The psychological variable that have been studies are those related to the controllability of stressors, predictability of stressors, and prior learning of helplessness. The present paper summarizes some experiments from the author's laboratory on such effects and also on some of the ways in which learning in the stressful situation affects physiological and/or behavioral responses.

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Up to the present time, serveral new approaches have been continued to produce the animal models with abnormal feeding, e.g., those besed on hypothalamic, genelic, endocrine, nutritional and drug-induced origins. However, most of the work on the model for abnormal feeding have been devoted to trying to disrupt the balance between food consumption snd energy expenditure and not to examine rhythmic processes of feeding. Chronically theophylline administered rats are considered to be a new type of the model displaying abnormal feeding due to the disruption of their circadian feeding as well as their impaired feeding motivation. This paper discussed the rhythmic and motivetional nature on abnormal feeding in the theophyllinzed model, since a model of this nature offers vaild one for interpretation of the causes of ingestive abnormalities. Suppression in dark time feeding as well as running-wheel activity was found in this model ratts, leaving daily food intake unaffected. These resalts of food intake and runnning activity were consisitent with change in the levels of srum glucose, fee fatty acid, insulin and lrtri glucose, which are the generally agreedupon substances to affect the reglation of food intake : i.e., those in the normal contorol rats were markedly dependent on a light-dark cycle, but not those in the model rats. The phases of the circadian activities of suxrase and maltase simply shifted half a day and no disappearance of their rhythmicities was absareved in the model. The model rats became less reactive to a relatively high concentration of dextrose and a moderate or a high concentration of quinine or saccharin. These changes in the feeding behavior and taste discrimination observed in this model reflect a circadian disruption of feeding, and an impairment of feeding motivetion which possibly modifies the circadian feeding pattern of the model as well. Further exploration of the conditions associated with circadian desynchronization of feeding in animals may provide insights into conditions related to abnormal feeding in man which lead to elucidate mechanims of regulation of food intake.

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Feeding behavior is regulated and conducted by the neuronal circuits of the lateral hypothalamus (LH) and the ventromedical hypothalamus (VMH) as main constiuents. We have been using the folloeing techniques in order to make clear the regulative system of feeding behavior neurophysiologically. One of them is the technique of applying chemicals directly to neurons by using the multi-barreled microelectrodes. Wehave been studying the action of acetylcholine, noradrenaline, dopamine and so on. Dopamin, in particular, may give us a clue to understand the pathophysiology of anorexia nervosa. The second in the way of studying the connection between the hypothalamus and other neural elements electrophysiolofically and by this technique we have made clear the morphological and functional relationship ofnthe frontal cortex the limbic system with LH. The thierd trchnique is to obserbe of neuronal sctivity in conscious animals druging food intake behavior. By this technique we can make clear where the motivation, the anticipation and the integration for feeding behavior are formed. But we cannot understand the whole regulative mechanism of feeding behavior only by subdividing the feeding behavior into the neuronal level. It is imporatant to associate this behavior with the result of stimulation experiments, destructive experiments, druginjection experiments and clinical cases in the future.

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Prolonged isolation from the early post-natal period may resalt in changes of brain composition such as receptor sensitivity enzyme activity as a resalt of a alterd monoamine turnover rate because of decreased neuronal activity following sensory deorivation. This change of composition may resalt in a behavioral change in isolated animals when the animals are exporsed to situations. If this hypothesis was demonstrated exparimentally, social isolation might become an interesting laboratory model for understanding the pathophysiology of psychosis like schizophrenia from the standpoint that psychosis consists of the interactions of both environmental influences and abnormal biological processes. The present study was undertaken to test this hypothesis. Male Wistar rats were isolated immediately after weaning for 12 weeks and exposed to electric foot shock of various intensities. The shock-elicited jumping behavior was measured every ten minutes for 1 hour. The frequency of jumping in isolated rats was lower than that in grouped and the difference between two groupes was the greatest with the most intence shock. In these experimental situations, there was no dignificant difference in monoamine turnover rate between the two groups while noradrenaline turnover markedly increased in both groups. Chlorpromazine supressed the jumping in a dose-dependent manner in both groups with stronger suppression in isolated rats. Methamphetamine facilitated the jumping in grouped rats dose-dependently while the drug rather depressed it in the isolated. From these results and the behavioral simikarity the isolated and 6-hydroxydopamine treated rats under foot shock situation, it was suggested that the receptor supersensitivity of central catecholamineragic neurons was involved in the behavioral change in isolated rats. Hopefully social isolation in rats might become an animal model of schizophrenia becaouse a considerable amount of the literatures on schizophrenia is concerned with the role of environment and experience in the pathogenesis and dopaminergic reseptor supersensitivity was noted recently about the pathophysicology of this disease.

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Differential effects of isolated housing (social deprivation), aggregated housing as well as olfactory bulbectomy were inverstigated from the standpoint of behavioral observation in rats and mice. A marked decrease was observed both in preening and grooming of general behaviors in rats by the treament of isolated housing for 4 weeks, but not in ambulation and reaing behaviors. Rats with olfactory bulbectomy (O. B. rats) which have increased locomotor activity, showed more higher elevation of ambulation and completely abolished preening or grooming behaviors when they were subjected to isolated housing. With the rats treated in this manner, the beginning of a higher increase in emotional response to stimuli was 2 weeks after the treatment of isolated housing, furthermore, such an increase was facilitated evidently by the additional treatment of olfactory removal. The active or passive conditioned avoidance responce of rats was inhibited by the treatment of isolated housing. From these results; distortions of emotionality such as disappearance of emotional stability, inhibition of conditioning behavior and hyperreactivity were observed by longterm isolation; furthermore, they were exaggerated by olfactory bulbectomy.

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The authors present a case of 51-years old female who has been suffering from a depressed mood and peripheral sensations of coolness due to SMON disease. In order to improve the pheral skin temperature through biofeedback and instrumental learning has been cited in literatures as a clinical tool for the control of migraine headaches and as a possible approach to Raynaud's disease. Two sensitive thermisters were mounted on the patient's toes. She was given light and meter feedback information to produce higher skin temperatures in the left foot compared to the right foot. Each training session consisted of two 20-min. trials which were separated by a 10-min. rest period. After 3 weeks of treatment, the patient's basal skin temperature, as measured on the left toe, increased from 23.1°to 29.5℃. The temperature change in the right toe was only 0.2℃ (30.2-30.0℃). The temperature difference between the two feet decreased from 7.1° to 0.5℃. In addition, she reporated that for the first time in 3 years, she had sensations of warmth in the feet. More than one year after treatment, the patient reported on continued relief from cool sensations. Persuasive though this case is, it will be too hasty to conclude that biofeedback is the sole therapeutic approach to the elimination of coolness of the feet. Carefully controlled studies would bring for the contributions to the treatment of peripheral vascular disorders, which could prove precise precise effectiveness of biofeedback training.

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