Role of Calcium Signaling in the Development of Prenatal Stress-Induced Functional Modifications of the Hypothalamo-Pituitary-Adrenal Axis

Abstract

We studied the effect of a blocker of calcium L-type channels, nimodipine, influencing rats within the prenatal period on the hormonal reaction of the adrenal glands (measured according to the level of corticosterone in the blood plasma) upon acute stress or upon injection of noradrenaline into the third cerebral ventricle in adult rat offspring (6- to 8-month-old males and females). Mothers in these animals were subjected daily to 1-hlong immobilization within the last week of pregnancy (from the 15th to 21th day). In males, prenatal stress weakened the adrenocortical reaction to acute stress immobilization, while in females such stress moderately intensified the above reaction. Peroral administration of 20 mg/kg nimodipin prior to immobilization of pregnant mothers prevented the development of the mentioned disturbances of the stress-related reaction of the hypothalamo-pituitary-adrenal axis (HPAA) in adult offspring of both sexes. Hormonal reaction of the adrenal cortex to injection of noradrenaline into the third cerebral ventricle of adult rat females, which was absent in prenatally stressed animals, was completely preserved after injection of nimodipin within the prenatal period. At the same time, nimodipin did not influence prenatal stress-induced changes in noradrenergic reactivity of the HPAA in adult males. Injection of nimodipine into pregnant mothers (which were not subjected to immobilization stressing) provided a modifying action on the formation of reactivity of the HPAA in adult offspring, which was manifested in prolongation of the adrenocortical reaction of the HPAA to intraventricular noradrenaline injection in males and females and also in moderate intensification of the hormonal response of the adrenal cortex to acute stress in females. The obtained data indicate that calcium-dependent mechanisms are significantly involved in the process of programming of prenatal stressinduced functional modifications of the HPAA in adult animals, while nimodipin exerts a protective effect with respect to these changes via weakening of calcium signalization in the cerebral regions involved in the control of the HPAA function.