GluR5-mediated glutamate signaling regulates hypothalamo-pituitary-adrenocortical stress responses at the paraventricular nucleus and median eminence.

Glutamate is the main excitatory neurotransmitter in the central nervous system, and plays an excitatory role in generation of hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. The current study assesses the role of kainate-preferring receptors in glutamatergic excitation of the HPA axis. In situ hybridization and immunohistochemical analyses confirmed the existence of the GluR5 kainate subunit in the paraventricular nucleus of the hypothalamus (PVN). Importantly, GluR5 immunoreactivity was enriched in the external lamina of the median eminence, where it is co-localized with corticotropin releasing hormone (CRH). Intra-PVN infusion of LY382884 increased plasma adrenocorticotropin (ACTH), corticosterone and PVN c-Fos immunoreactivity. Infusions of LY382884 into the median eminence region, on the other hand, reduced restraint induced ACTH release without altering c-Fos expression. Together, these findings provide evidence for glutamate-mediated signaling in control of CRH release at the PVN and median eminence, mediated by way of kainate-preferring receptor complexes.

Daily limited access to sweetened drink attenuates hypothalamic-pituitary-adrenocortical axis stress responses.

Stress can promote palatable food intake, and consumption of palatable foods may dampen psychological and physiological responses to stress. Here we develop a rat model of daily limited sweetened drink intake to further examine the linkage between consumption of preferred foods and hypothalamic-pituitary-adrenocortical axis responses to acute and chronic stress. Adult male rats with free access to water were given additional twice-daily access to 4 ml sucrose (30%), saccharin (0.1%; a noncaloric sweetener), or water. After 14 d of training, rats readily learned to drink sucrose and saccharin solutions. Half the rats were then given chronic variable stress (CVS) for 14 d immediately after each drink exposure; the remaining rats (nonhandled controls) consumed their appropriate drinking solution at the same time. On the morning after CVS, responses to a novel restraint stress were assessed in all rats. Multiple indices of chronic stress adaptation were effectively altered by CVS. Sucrose consumption decreased the plasma corticosterone response to restraint stress in CVS rats and nonhandled controls; these reductions were less pronounced in rats drinking saccharin. Sucrose or saccharin consumption decreased CRH mRNA expression in the paraventricular nucleus of the hypothalamus. Moreover, sucrose attenuated restraint-induced c-fos mRNA expression in the basolateral amygdala, infralimbic cortex, and claustrum. These data suggest that limited consumption of sweetened drink attenuates hypothalamic-pituitary-adrenocortical axis stress responses, and calories contribute but are not necessary for this effect. Collectively the results support the hypothesis that the intake of palatable substances represents an endogenous mechanism to dampen physiological stress responses.