Glucocorticoid hypersecretion following intracerebroventricular injection of ethylcholine mustard aziridinium ion in rats

To investigate whether cholinergic hypofunctions in the brain influence hyp othalamic-pituitary-adrenal activity, we examined the effects of cholinergi c neurotoxin ethylcholine mustard aziridinium ion on basal and stress-induc ed levels of corticosterone in rats. Blood sampling from rats following int racerebroventricular injection of saline (5 mul, as a control) or this neur otoxin (5 nmol/5 mul) was performed over a day in one series, and was taken before, during and after an immobilization stress exposure in another seri es. Plasma levels of corticosterone and adenocorticotropin were determined by the radioimmunoassay. The basal levels of plasma corticosterone and adre nocorticotropin over a day were significantly higher in the neurotoxin-trea ted rats, compared with the control rats (corticosterone, P < 0.001; adreno corticotropin, P < 0.05). Further, relative adrenal gland weight of the neu rotoxin-treated rats was significantly greater than that of the control rat s (P < 0.05). However, responses in plasma corticosterone level caused by t he immobilization stress in the neurotoxin-treated rats were not different from those in the control rats. The present study demonstrated that damage to the cholinergic neurons in th e brain increased hypothalamic-pituitary-adrenal activity over a day, proba bly due to Freedom from inhibitory influences of the hippocampal cholinergi c system, but that this damage did not influence stress-induced changes in plasma glucocorticoid level. (C) 2001 IBRO. Published by Elsevier Science L td. All rights reserved.