Effects of acute and prolonged administration of chlordiazepoxide upon the pituitary-adrenal activity and brain catecholamines in sound stressed and unstressed rats

We have studied the effects of chlordiazepoxide upon the pituitary-adrenal activity (evaluated by the levels of serum corticosterone), and brain catecholamines in rats exposed to sound stimulation of 500 cycles per second at 110 decibels for 15 min. The sound stimulus itself induced a 3-fold rise in the serum corticosterone level. Acute administration of chlordiazepoxide to rats not subjected to sound stimulation induced significant increases in serum corticosterone levels; this effect was dose-dependent in the dose range of 5 to 25 mg/kg. An inhibition of the stress response was observed in rats injected acutely with the drug in doses ranging from 5 to 15 mg/kg and subjected to sound stimulation. Development of tolerance to the acute effects of the drug on the pituitary-adrenal activity was observed. Brain dopamine and noradrenaline levels showed a significant decrease after acute administration of some of the drug doses, but a dose-related effect was never observed. Prolonged treatment with chlordiazepoxide does not significantly affect the levels of either dopamine or noradrenaline at any duration of treatment.The results point to the possibility that the sites in the central nervous system mediating the depressant action of chlordiazepoxide and those mediating the anxiolytic action influence the pituitary-adrenal activity in an opposite fashion: the depressant in a stimulatory way and the anxiolytic in an inhibitory way. However, the mechanisms of tolerance development to the stimulatory or inhibitory action of chlordiazepoxide on the pituitary-adrenal activity seem to be alike.