Cholinergic influences on hypothalamic-pituitary-adrenocortical activity of stressed rats: an approach utilizing choline deficient diets.

Male rats were placed on choline (Ch) deficient diets for 3 to 14 days, without and with Ch (normal and large doses) supplemented in the drinking water, to determine whether altering the availability of Ch would affect the cholinergic system in relation to the latter's role in modulating the hypothalamic-pituitary-adrenocortical (HPA) system of non-stressed and stressed animals. The results indicate that the basal nonstressed activity of the HPA system, as assessed by adrenal and plasma corticosterone concentrations, was not affected by placing the animals on these diets for as long as 14 days. Furthermore, the in vitro production of corticosterone by these adrenal glands, in the presence or absence of adrenocorticotrophin, was similar to those observed in animals on the regular rat diet; however, the HPA responses to auditory (100 db) stress, and to a lesser extent hypercapnic (9% CO2) stress, were impaired on the Ch deficient diet (14 days), and these responses were partially corrected by supplementing the diet with Ch in the drinking water. Thus, the data suggest that altering the dietary intake of Ch may affect cholinergic activity, which in turn affects the HPA response to stressors.

Cholinergic influences on hypothalamic-pituitary-adrenocortical activity of stressed rats: an approach utilizing agonists and antagonists.

Cholinergic involvement in the regulation of the hypothalamic-pituitary-adrenocortical (HPA) system of male rats was evaluated using muscarinic (atropine and methacholine) and nicotine (mecamylamine and nicotine) agents, which were selected for their specificity on cholinergic receptors (ChR). They were administered either intracerebroventricularly (icv) to produce central effects, or ip to produce both central and peripheral effects, prior to subjecting the animals to either auditory or hypercapnic stress for 1 h. Plasma corticosterone was used as an index of HPA activity. The results suggest that central muscarinic ChR are involved in inhibiting HPA activity in both non-stressed and stressed animals, whereas central nicotinic ChR are excitatory during stress but inactive in the non-stressed state. Stimulation of peripheral nicotinic ChR appeared to potentiate the HPA response to hypercapnia, and to inhibit the central excitatory nicotinic ChR when the latter were activated in non-stressed and auditory stress rats. These data suggest that during auditory stress the HPA system is more dependent upon the cholinergic system for its activation than during non-stressed and hypercapnic states.

Adrenal and plasma corticosterone of hepatectomized rats: responses during hepatic restoration.

Adrenal and plasma corticosterone concentrations of partially (70%) hepatectomized male rats were examined during the course of liver restoration. Following hepatectomy, 33% of the liver mass observed in the sham operated group was present on day ), with approximately 50, 70, 75 and 82% present on days 2, 3, 4 and 7, respectively. Total restoration was noted by day 14. Plasma proteins abruptly decreased after hepatectomy and then gradually increased as liver mass was restored. The weights of both adrenal glands of hepatectomized animals were increased markedly on days 1 to 3, while adrenal corticosterone concentrations and production were elevated on day 2. Plasma corticosterone levels increased significantly following hepatectomy and remained elevated for 4 days, whereas only on the first day after surgery were the adrenal and plasma corticosterone levels elevated in the sham operated group. These data suggest that, despite the loss of liver mass and hence the apparent loss of delta 4-steroid hydrogenase activity, the adrenal glands do not decrease but actually increase their secretion during the first few days after hepatectomy.

Actions of cholinergic agonist and antagonists on the adrenocortical response of basal, hypoxic, and hypercapnic rats.

Cholinergic neuronal influences on the function of male rat's hypothalamo-hypophyseal-adrenocortical (HHA) system both during basal and stressful situations (hypoxia and hypercapnia) were investigated using a cholinergic agonist (eserine) and antagonists (atropine, methyl atropine, mecamylamine and 4-(1-naphthylvinyl) pyridine). The results indicate that the transmitter, acetylcholine (ACh), plays a partial role in the regulation of the HHA system. The muscarinic (m) effects of ACh were stimulatory peripherally and inhibitory centrally. The nicotinic (n) effects were stimulatory and possibly affected the HHA system by inhibiting the central m-inputs. The cholinergic regulation of the HHA system for both non-stressed and hypercapnic animals is probably mediated via a common nm-cholinergic pathway.

Adrenocortical responses of rats to acute hypoxic and hypercapnic stresses after treatment with aminergic agents.

Monoaminergic influences on the regulation of the hypothalamo-hypophyseal-adrenocortical (HHA) system during acute stresses (hypoxia and hypercapnia) were investigated in male rats. Plasma corticosterone levels were used to assess HHA activity, and the alterations in monoaminergic activity were induced by pretreating the animals with various pharmacologic agents (reserpine, alpha MT, FLA-63, pCPA, L-Dopa, pargyline, Lilly 110140, phentolamine and propranolol). Dexamethasone-treated rats were utilized to assess the site at which these monoaminergic substances acted. The latter experiments showed that these agents did not have a marked effect directly on the adrenal cortex and thus the site(s) of action was at the level of the anterior pituitary and/or above. Altering the serotoninergic system did not appreciably influence the HHA response to hypoxia and hypercapnia, whereas increasing the activity of the adrenergic system partially prevented the rise usually observed in plasma corticosterone levels during these stresses. These data suggest that different aminergic pathways may be utilized for different stresses.