Neuropeptide Y1 receptor is a key element in stress response to food deprivation (1126.7)

Abstract

The hypothalamic‐pituitary adrenal (HPA) axis functions as a default pathway for the maintenance of energy homeostasis. Food restriction or deprivation leads to prolonged HPA axis activation but the exact mechanism of this continuous HPA activation is not yet well understood. Our experiments were designed to determine whether neuropeptide Y (NPY) Y1 receptors participate in the stress response to food deprivation since NPY expression is elevated during periods of fasting. Food deprivation of male rats for 24 hours caused weight loss, adrenal gland hypertrophy and increased plasma ACTH and corticosterone concentrations. Food deprivation increased NPY mRNA expression in arcuate and brainstem C2/A2 nuclei areas that are known to project to the hypothalamic paraventricular nucleus (PVN). While the total area of CRH mRNA positive cells in the PVN decreased during food deprivation, the CRH mRNA signal intensity increased in the remaining active cells. Food deprivation also increased pCREB‐ir expression in PVN, an indication for neuronal activation. A majority of pCREB‐positive cells were CRH/Y1‐ir neurons. Infusion into the PVN of 1 nmol BIBP3226, a specific Y1 receptor antagonist, eliminated the elevated corticosterone blood levels in food‐deprived animals. Our observations support the notion that hypothalamic NPY Y1 receptors expressed by CRH neurons are pivotal for triggering a strong stress response during periods of food deprivation.Grant Funding Source: Supported by NIMH 62621