Effect of Chlordiazepoxide on Eosinopenia of Stress in Rabbits

Abstract

CHLORDIAZEPOXIDE, a new psychotherapeutic drug, chemically unrelated to either phenothiazine derivatives or indole–alkaloid derivatives, has been reported to show a number of pharmacological activities¹. A possible hypothalamic activity of chlordiazepoxide has been reported². We have investigated the effect of this drug on a physiological activity controlled by the hypothalamus, that is, eosinopenia after emotional stress. The emotional stress was applied to rabbits weighing 1.5–2 kg by the method of O'Conor and Verney as adopted by Colfer et al.³. Blood samples were taken from the ear veins of rabbits once before and again 3.5 h after the emotional stress (electric shock) was administered. The strength of the stimulus given by an electronic stimulator was such that it produced signs of fright in the animal. A freshly prepared solution of chlordiazepoxide (50 mg/kg) was given intraperitoneally 0.5 h before the electric shock and by this time the animal was showing the tranquillizing effect of the drug. Electrical stimulus was not repeated for 2 days. After pretreatment with chlordiazepoxide the rabbits still showed signs of fright after a similar electric shock. The experiments were carried out on three rabbits, each animal acting as its own control. Average means of blood counts are as follows. Before administration of drug and stimulus, total white blood cell count was 4,860/cm, and the total number of eosinophils was 486 (10 per cent)/cm. Total white blood cell count 3.5 h after electric shock was 6,187/cm (a rise of 28.5 per cent), and the total number of eosinophils was 309.35 (5 per cent)/cm (a significant fall). Total white blood cell count 3.5 h after administration of chlordiazepoxide and electric shock was 5,175/cm (a rise of 6.4 per cent), and the total number of eosinophils was 466/cm (8.25 per cent, no significant change).