Intranasal Administration of Neuropeptide Y Significantly Antagonized Chronic Stress Responses via Central Gabaa Receptors in Male Rats

Abstract Stress is widely believed to play a major role in the pathogenesis of many diseases. Central neuropeptide Y (NPY) counteracts the biological actions of corticotropin-releasing factor (CRF), and in turn attenuates stress responses. Administration (intracerebroventricular, ICV) of NPY, significantly antagonized the inhibitory effects of chronic complicated stress (CCS) on gastrointestinal (GI) dysmotility in rats. However, ICV administration is an invasive technique. The effect of intranasal administration of NPY on the hypothalamus-pituitary-adrenal (HPA) axis and GI motility in CCS conditions have not been studied, and the inhibitory mechanism of NPY on CRF through the gamma-aminobutyric acid (GABA)A receptor needs to be further investigated. A CCS rat model was set up, NPY was intranasal administered every day prior to the stress loading. Further, a GABAA receptor antagonist was ICV injected daily. Central CRF and NPY expression were evaluated, serum corticosterone and NPY levels were analyzed, and colonic motor functions was assessed. CCS rats showed significantly increased CRF expression and corticosterone levels, which resulted in enhanced colonic motor functions. Intranasal NPY significantly increased central NPY mRNA expression and reduced central CRF mRNA expression as well as the plasma corticosterone level, helping to restore colonic motor functions. However, ICV administration of the GABAA receptor antagonist significantly abolished these effects. Intranasal administration of NPY upregulates the hypothalamic NPY system. NPY may, through the GABAA receptor, significantly antagonize the overexpressed central CRF and attenuate the HPA axis activities in CCS conditions, exerting influences and helping to restore colonic motor function.