Effect of chlordiazepoxide on stress in rats

1,4-benzdiazepine derivatives do not influence endocrine functions even when they are administered on a long-term basis, because of their known low toxicity and good tolerance.

Abstract

It is known that stress is accompanied by an increased level of corticosteroids in the blood. If tranquilizers are administered prior to stress, then according to some authors the production of 17-hydroxycorticosteroids by adrenal is decreased /1/. Kivalo and Rinnen /2/ have found that perphenazine decreased production of ascorbic acid in adrenals of stressed rats. The effect of chlorpromazine on production of adrenocorticotropic hormone /ACTH/ has been studied by Mahfouz and Ezz /3/, Holzbauer and Vogt /4/, Nasmyth /5/. However the results are considerably discrepant. It has been reported that production of ACTH is elevated /4,5/ or depressed /3/ when chlorpromazine is administered to the animals. Smith et al. /6/ observed decreased concentration of ascorbic acid in adrenals and increased level of corticosterone in plasma after the administration of promazine, chlorpromazine, chlorpromazine sulfoxide and trifluorpromazine. These observations was interpreted by them as the sign of hyposecretion of ACTH caused by studied agents. The studies of Superstinnen and Sulman /7/ and that of Boris et al. /8/ have shown that 1,4-benzdiazepine derivatives do not influence endocrine functions even when they are administered on a long-term basis. The toxicity of these derivatives is low, their LD50 being in the range of several hundred to one thousand mg/kg body weight. We have used the derivatives of 1,4-benzdiazepine for the study of their effect on stressed animals, because of their known low toxicity and good tolerance. Furthermore, they do not influence the function of adrenals the activity that we have used for the evaluation of stress.