Effects of Psychotropic Drugs on Switch‐Off Behavior in the Cat

Field: Neuroscience (Life Sciences)

SUMMARY To study the mechanism of action of psychotropic drugs by using the switch‐off behavior (SOB) produced by stimulation of the antero‐medial hypothalamus of the cat as index, experiments were performed on 72 adult cats carrying chronically implanted electrodes in the antero‐medial hypothala mus and other cortical and subcortical structures. To induce the SOB, monopolar stimulation with 60 Hz A.C. current was delivered on the hypothalamus with the random interval of 3–8 min, and three degrees of stimulus intensity, i.e ., intensity 1 (weak), 2 (medium) and 3 (strong) were used. To exclude the influence of the drug‐induced sleep‐like process on the SOB, the experiment was performed, beside the one under natural condition, also after awakening the cat by delivering sensory arousal stimulation. Drugs used in this experiment were 5 and 10 mg/kg chlorpromazine (CPZ) i.m . as major tranquilizer, 5, 10 and 15 mg/kg imipramine (IMP) i.m . as a thymoleptica, and 1 mg/kg diazepam (DZP) i.p . as a minor tranquilizer. The effects of drug on the response time of the SOB were ob served. The rate of prolongation of the response time following CPZ administration was highest in the experiment with stimulus intensity 1 (weak), and became lower as the intensity of stimulus became stronger. The rate of prolongation of response time under 10 mg/kg CPZ was much higher than that under 5 mg/kg CPZ administration. When the animal was aroused by sensory stimulation, the response times became shorter than those without arousal stimulation, but they were still much higher than control values. The response time of the SOB was also increased under administration of IMP. The rate of prolongation of the response time with 5 mg/kg IMP administration was high in order of intensity 2, 1 and 3. In the SOB experiment with 10 mg/kg IMP, the rate of prolongation was higher than that in the experiment with 5 mg/kg IMP, but almost equal at each stimulus intensity. Ad ministration of 15 mg/kg of IMP, prolonged the response time most markedly. The response time was lengthened by IMP in both experiments with and without sensory arousal stimulation. But when the animal was aroused by sensory stimulation the degree of shortening of the response time was much greater than in the case of CPZ experiment, though the mean value of the response time was slightly higher than control value. It was shown that, in the case of IMP, the influence of the sleep‐like process induced by IMP plays a considerable role for the prolongation of the response time of the SOB. Administration of DZP tended to shorten the response time of the SOB. No significant difference in response time was observed between the experiments with and without sensory stimulation, To exclude the possibility that the prolongation of the response time under ad ministration of CPZ and IMP is not caused by the inhibition of the drive formation but due to the disturbance of motor function, the response time was divided into drive time and performance time and each was measured independently. It was revealed that motor function was influenced slightly under CPZ administration, but the prolongation of the response time was mainly attributed to the increase of drive time, that is, to the suppression of the function of drive formation. From the results mentioned above, it was concluded that the SOB seemed to be a useful tool to investigate the mechanism of action of psychotropic drugs. CPZ was sup posed to exert an inhibitory action directly on the hypothalamus, whereas the action of IMP on the hypothalamus is much weaker than that of CPZ. The enhancement of SOB by DZP might be due to a release phenome non induced by suppression of limbic function.