Mechanisms regulating inhibition of the hypothalamic-pituitary-adrenal axis during restriction-induced drinking in the rat

Classically, inhibition of the hypothalamic-pituitary-adrenal (HPA) axis is believed to occur through hormonal negative feedback mechanisms, in which corticosteroids produced by the adrenal gland act at the level of the brain and pituitary to limit their own production. However, studies in the rat have suggested that the HPA axis can be rapidly inhibited by mechanisms that are independent of corticosterone negative feedback, and that are initiated at the level of the central nervous system. These studies have shown that the act of restriction-induced eating or drinking leads to the rapid inhibition of corticosterone production by the adrenal gland. The focus of this thesis was to investigate the efferent mechanisms responsible for this suppression of corticosterone after restriction-induced drinking. To accomplish this goal, several hypotheses were tested, with each hypothesis examining the contribution of a factor known to affect plasma corticosterone. The studies presented here suggest that moderate elevations in plasma vasopressin induced by dehydration can stimulate adrenal corticosterone production independently of ACTH and that the decrease in plasma corticosterone that occurs after restriction-induced drinking is due, in part, to a concomitant decrease in plasma vasopressin as magnocellular neuronal activity is reduced. In addition, a reduction in plasma ACTH and an increase in plasma corticosterone are likely to contribute to the decline in plasma corticosterone after drinking. It is possible that a reduction in adrenal sensitivity, at least to ACTH, contributes to this response as well; whether or not this effect is mediated by innervation of the adrenal cortex remains to be determined. Future investigations could reveal if the suppression of corticosterone after restriction-induced drinking is a response to a reduction in physiological drive (i.e. removal of osmotic stress), or if it is the result of activating inhibitory limbic pathways to the HPA axis (i.e. reward).