Subdiaphragmatic vagotomy prevents drinking-induced reduction in plasma corticosterone in water-restricted rats.

Dehydrated rats exhibit a rapid inhibition of the hypothalamic-pituitary-adrenal axis after rehydration. Drinking activates vagal afferents that project to neurons in the nucleus tractus solitarius (NTS). We hypothesized that when dehydrated rats drink, vagal afferents stimulate NTS neurons initiating inhibition of hypothalamic-pituitary-adrenal activity. Experiments assessed NTS activity by measuring Fos expression. Rats were water restricted for 1 or 6 d, limiting access to water to 30 min/d in the morning. Drinking after single or repeated restriction increased Fos, demonstrating increased NTS activity. We next examined the contribution of the vagus by comparing hormonal responses after total subdiaphragmatic vagotomy or sham surgery. Water restriction for 6 d increased plasma arginine vasopressin (AVP), ACTH, and adrenal and plasma corticosterone in both groups. In sham rats, drinking reduced plasma AVP, ACTH, adrenal and plasma corticosterone by 7.5 min. In total subdiaphragmatic vagotomy rats, whereas drinking reduced plasma AVP, ACTH, and adrenal corticosterone, drinking did not reduce plasma corticosterone. To identify the source of vagal activity, hormonal responses to restriction-induced drinking were measured after common hepatic branch vagotomy (HBV). Although pituitary hormonal responses were not affected by HBV, the adrenal and plasma corticosterone responses to water restriction were reduced; in addition, drinking in HBV rats decreased adrenal corticosterone without changing plasma corticosterone. These data indicate that an intact vagus is necessary to reduce plasma corticosterone when water-restricted rats drink and that the common hepatic vagal branch contributes to the response. These findings implicate the vagus in augmenting rapid removal of circulating corticosterone during relief from stress.

Differential regulation of parvocellular neuronal activity in the paraventricular nucleus of the hypothalamus following single vs. repeated episodes of water restriction-induced drinking.

Acute activation of the hypothalamic-pituitary-adrenal (HPA) axis releases glucocorticoids to maintain homeostasis, whereas prolonged exposure to elevated glucocorticoids has deleterious effects. Due to the potential benefits of limiting stress-induced glucocorticoid secretion, the present study uses drinking in dehydrated rats as a model to delineate mechanisms mobilized to rapidly inhibit HPA activity during stress. Using Fos expression as an indicator of neuronal activation, the effect of a single or repeated episode of dehydration-induced drinking on the activity of magnocellular and parvocellular neurons in the paraventricular nucleus (PVN) of the hypothalamus was examined. Adult male rats underwent a single episode or repeated (six) episodes of water restriction and were sacrificed before or after drinking water in the AM. Plasma osmolality, vasopressin (AVP), adrenocorticotropic hormone (ACTH) and corticosterone were elevated by water restriction and reduced after drinking in both models. Fos expression was elevated in AVP-positive magnocellular PVN neurons and AVP- and corticotropin releasing hormone (CRH)-positive parvocellular PVN neurons after water restriction. Fos expression was reduced in magnocellular AVP neurons after both models of restriction-induced drinking. In contrast, Fos expression did not change in AVP and CRH parvocellular neurons after a single episode of restriction-induced drinking, but was reduced after repeated episodes of restriction-induced drinking. These data indicate that drinking-induced decreases in glucocorticoids in dehydrated rats involve multiple factors including reduction in magnocellular release of vasopressin and reduction in parvocellular neuronal activity. The differential inhibition of PVN parvocellular neurons after repeated rehydration may reflect a conditioned response to repeated stress reduction.

Dehydration-induced drinking decreases Fos expression in hypothalamic paraventricular neurons expressing vasopressin but not corticotropin-releasing hormone.

Water-restricted (WR) rats exhibit a rapid suppression of plasma corticosterone following drinking. The present study monitored Fos-like immunoreactivity (Fos) to assess the effect of WR-induced drinking on the activity of vasopressin (VP)-positive magnocellular and parvocellular neurons and corticotropin-releasing hormone (CRH)-positive parvocellular neurons in the paraventricular nucleus of the hypothalamus. Adult male rats received water for 30 min (WR) in the post meridiem (PM) each day for 6 days and were killed without receiving water or at 1 h after receiving water for 15 min. In WR rats, Fos increased in VP magnocellular and parvocellular neurons but not CRH neurons. After drinking, Fos was reduced in VP magnocellular and parvocellular neurons but did not change in CRH neurons. To assess the severity of osmotic stress, rats were sampled throughout the final day of WR. Plasma osmolality, hematocrit and plasma VP were increased throughout the day before PM rehydration, and plasma ACTH and corticosterone were elevated at 1230 and 1430, respectively, showing that WR activates hypothalamic-pituitary-adrenal activity during the early PM before the time of rehydration. To determine the effects of WR-induced drinking on CRH neurons activated by acute stress, WR rats underwent restraint. Restraint increased plasma ACTH and corticosterone and Fos in CRH neurons; although rehydration reduced plasma ACTH and Fos expression in VP neurons, Fos in CRH neurons was not affected. These results suggest that inhibition of VP magnocellular and parvocellular neurons, but not CRH parvocellular neurons, contributes to the suppression of corticosterone after WR-induced drinking.

Adrenal splanchnic innervation contributes to the diurnal rhythm of plasma corticosterone in rats by modulating adrenal sensitivity to ACTH.

Activity of the hypothalamic-pituitary-adrenal axis is characterized by a diurnal rhythm with an AM nadir and PM peak. Splanchnic nerve transection disrupts the diurnal rhythm in plasma corticosterone; however, there is a controversy as to whether the nerve-mediated effect is 1) via inhibition in the AM vs. excitation in the PM, or 2) involves changes in adrenal sensitivity to ACTH. The present studies were designed to address these issues. Adult male rats were anesthetized and underwent bilateral transection of the thoracic splanchnic nerve or sham transection. One week after surgery, rats were killed in the AM or PM with collection of nonstress plasma for measurement of corticosterone and ACTH. Plasma corticosterone was increased in the PM relative to the AM; however, plasma corticosterone in the PM was attenuated by splanchnic nerve transection, without affecting plasma ACTH. This decrease in PM plasma corticosterone after nerve-transection was 1) associated with decreased adrenal responsivity to ACTH, 2) associated with decreased adrenal cAMP content, 3) prevented by adrenal demedullation, and 4) not affected by removal of adrenal capsaicin-sensitive afferent fibers. Repeated serial blood sampling from individual rats confirmed the excitatory effect of splanchnic innervation in the PM. These results support the hypothesis that the adrenal splanchnic innervation modulates the diurnal rhythm in plasma corticosterone by increasing adrenal responsivity to ACTH and augmenting steroidogenesis in the PM and suggest that alterations in adrenal corticosterone secretion obscured by pulsatile secretion are more clearly revealed with repeated serial blood sampling.

Neural circuitry in the regulation of adrenal corticosterone rhythmicity.

Adrenal cortical secretion of glucocorticoids is an essential adaptive response of an organism to stress. Although the hypothalamic-pituitary-adrenal axis regulates the adrenal cortex via release of ACTH, there is strong evidence supporting a role for sympathetic innervation in modulating adrenal glucocorticoid secretion. The dissociation between changes in ACTH and glucocorticoids under non-stress and stress conditions has reinforced the concept that neural control of the adrenal cortex acts to modulate steroidogenic responses to circulating ACTH. A dual control of the adrenal cortex has been implicated in the prominent circadian rhythm in glucocorticoids. However, the central neural substrate for circadian changes in glucocorticoids that are mediated by peripheral neural innervation of the adrenal cortex has not been conclusively delineated. The hypothesis to be addressed is that neurons in the paraventricular nucleus of the hypothalamus receive input from the suprachiasmatic nucleus and project to sympathetic preganglionic neurons in the spinal cord to provide inhibitory and excitatory input to the adrenal cortex that drives the circadian rhythm. This review examines anatomical and physiological evidence that forms the basis for this putative neural circuit.