[Application of group psychology of animals into pharmacological studies. 12. Specificities of actions of psychotropic drugs on emotional and exploratory behaviors of a single mouse or groups of 2 or 3 animals].

The exploratory movement recorder of Tokyo University of Education type was utilized to assess the exploratory motor activity of groups of 1, 2 and 3 mice of the dd-strain. As the animals were observed during 15 min periods to move spontaneously, psychotropic drugs were administered and the specific actions of these agents were determined. Each drug was given i.p. in a dose which proved non-effective in a single mouse. Observations were as follows: The ratio of exploratory motor activity of each pair of mice as compared to a single mouse was not always different from that of control animals. When a 3rd mouse was added to the pair, the motor activity either increased or decreased considerably. The rate of increase in motor activity was calculated 45 min after caffeine, pentetrazol, ephedrine and DL-amphetamine and was found to be less than in the control animals. After administration of chlordiazepoxide, diazepam, imipramine, chlorpromaxine or mescaline, the rate of increase in motor activity was considerably greater than in the controls. With dimorphoramine or hexobarbital, the rate was much the same as control. After beta-oxy gamma-aminobutyric acid, the rate was slightly increased and with diphenhydramine the rate was slightly less than control. Thus the exploratory motor activity of 3 mice as compared to that of 2, decreased considerably after administration of psychotropic stimulants, while after psychotropic depressants, an even greater increase was observed. We have already reported on the mutual relation of mice in fighting episodes and E1-mice convulsions. Those relations were, however, responses elicited by the physical stimulation. In contrast, the mutual relation in this paper is more of a natural nature. In view of observations in this paper, it is considered that CNS stimulants increase the mutual, emotional, checking behavior in groups of 3 animals while CNS depressants decrease the checking behavior. Such behavior is one example of the emotional conduct when a 3rd party is added to a 2 member group.

[Application of animal mass psychology to pharmacology (XI). The role of light in the induction of convulsions in E1-mice].

In preliminary experiments to investigate the influence of masking the eyes of E1-mice on the rate of non-convulsions (RNC), it was suggested that the quantity of light as well as visibility itself played a role in inducing convulsions. The following experiments were thus carried out: (a) Both TSC (the threshold of number of shakings required for induction of convulsions) and RNC increased remarkably on the 5th day after enucleation of bilateral eyeballs from E1-mice, but 15 days later recovery to control level was observed. Moreover, TSC and RNC at 2 p.m. increased considerably compared with the control, however, the increase was rarely observed at 10 a.m.. (b) 2 groups of E1-mice reared intact under radiation of light plus different time schedules were shaken at 10 a.m. and 2 p.m., respectively. Consequently, TSC after radiation for 5 hours was less than that after radiation for 1 hour. When observed 9 hr after radiation, TSC could not be differentiated from TSC at 5 hr after the radiation. (c) E1-mice were reared under continuous lighting, continuous darkness or a normal lighting situation, after which TSC and RNC were examined. From our observations, the intensity of light appears to play a role in inducing convulsions. (d) When mice were shaken immediately after lighting, RNC decreased in inverse proportion to increase in the quantity of light. TSC was not influenced by the luminosity itself. One hour after lighting, however, the influence of lighting had disappeared. The intensity, quantity or irradiation time would not, however, influence the induction of E1-mice convulsions so much as the cognizance of light by the individual animals. Such a conception is derived from the "cognitive theory" in psychology.

[Stress state caused by alteration of rhythms in environmental temperature, and the functional changes in mice and rats].

Exactly how the organic mechanism corresponds to variations of environmental temperature has not been clarified and for elucidation we reared mice and rats under the conditions of alterating rhythm in temperature (ART). Mice (or rats) were reared at a temperature of 24 degrees C and 8 degrees C (or -3 degrees C) every hour continuously from 10 a.m. to 5 p.m. and at 8 degrees C (or -3 C) from 5 p.m. to the following 10 a.m. Severe stress was evidenced in the animals and was termed specific ART-stress (SART-stress). In this type of stress, there was no apparent increase in body weight, respiration and heart rate were increased slightly and the QRS-time on the ECG was prolonged. ACh sensitivity of the isolated duodenum tested by the Magnus method in SART-stress mice was found to have declined considerably as compared to the normal. Histological observation of the SART-stress rats revealed that the wet weight of the spleen was lighter than that of the controls, while that of the lungs, heart, liver, stomach, kidneys and adrenal glands was close to that of control. Macroscopically, red brown spots of the lungs were visible. Ventricular hypertrophy, slight erosion and hyperemia were present in the interior of the stomach. On the galvanic skin response (GSR) test, electrical resistance of the skin of SART-stress rats was less than that of normal rats and the rate of increase of resistance caused by external stimulus was greater. Recovery time from change in GSR was shorter than in normal animals. Consequently, SART-stress appears to be a form of disease and sudden changes in temperature even in humans may contribute to this state.

[Effect of neurotropin on SART stress (stress caused by alteration of rhythms in environmental temperature) in mice and rats].

We reported previously that by altering the rhythm of environmental temperature (ART) the physiological mechanism was changed to an abnormal state which we termed specific ART-stress (SART-stress). In the present report, the effects of neurotropin and other tranquilizers on this SART-stress state were investigated. Neurotropin is an extract containing many conjugated polysaccarides isolated from the skin or tissues of rabbits which had been inoculated with the living cowpox virus. Neurotropin prevented the decrease in body weight of both mice and rats caused by the SART-stress. However, there was no such prevention when an extract isolated from vaccinia virus-uninjured, healthy rabbit skin was given. Chlorpromazine (Cp), reserpine (Rp), diazepam (DZ), imipramine or diphenhydramine gave no protection against the decrease in body weight. Slight increase in number and variation of respirations in SART-stress animals was to some extent prevented by neurotropin. Prolongation of the QRS interval was restored to control with the administration of the above mentioned drugs. Decrease in ACh sensitivity of the isolated duodenum tested by the Magnus-method was prevented by neurotropin. In the galvanic skin response test in rats, decrease in electric resistance on the skin, increase in reactivity and shortening of reaction time caused by SART-stress was prevented to the greatest extent by neurotropin and also to a considerable degree by parenteral administration of DZ or beta-hydroxy gamma-aminobutyric acid (GABOB), the effective results of the drugs being: Neurotropin, DZ, GABOB in that order. Cp and Rp, major tranquilizers were found to be the least effective.

[Relation of time of administration of drugs to their acute toxicity to experimental animals].

The circadian rhythms of acute toxicity of N-methyl D-aspartic acid, picrotoxin, pentetrazol, strychnine, chlorpromazine and Na-methylhexabital in dd-mice were investigated. The drugs were injected into mice on the hour at 2, 6, 10, 14, 18 or 22 in one day, after which the cumulative mortalities were calculated for 72 hours. Regarding central stimulants, the mortality of mice injected at 22 (o'clock) was lowest, and when injections were given at 2, 10 or 18 (o'clock), the mortality was higher than at any other time. On the other hand, regarding central depressants, the mortality was lowest at 10, and highest at 14 or at 18 o'clock. Thus, the administration time of central stimulants showing the lowest mortality was shifted about 12 hours in comparison with central depressants. As compared to the central depressants, the mortality rate as the result of central stimulants showed a great contrast when injected at 10 o'clock.