Publications

Abstract

BACKGROUND AND PURPOSE: Exposure to an acute stress inhibits gastric emptying and stimulates colonic transit via central neuropeptide Y (NPY) pathways; however, peripheral involvement is uncertain. The anxiogenic phenotype of NPY(-/-) mice is gender-dependent, raising the possibility that stress-induced gastrointestinal (GI) responses are female-dominant through NPY. The aim of this study was to determine GI transit rates, corticosterone levels and food intake after acute restraint (AR) or novel environment (NE) stress in male and female NPY(-/-) and WT mice. EXPERIMENTAL APPROACH: Upper gastrointestinal transit (UGIT) (established 30 min after oral gavage) and corticosterone levels were determined under basal or restrained conditions (30 min) and after treatment i.p. with Y(1) antagonist BIBO3304 or Y(2) antagonist BIIE0246. Faecal pellet output (FPO) was established after AR and treatment i.p. with NPY in the NE, as were colonic bead expulsion rates. KEY RESULTS: UGIT and FPO were similar in unrestrained male and female mice. NPY(-/-) females displayed significantly slower UGIT than NPY(-/-) males after AR, but both genders displayed significantly higher FPO and reduced food intake relative to WT counterparts. Peripheral NPY treatment increased bead expulsion time in WT mice. AR male NPY(-/-) mice had higher levels of corticosterone than male WT mice; whilst in AR WT mice, after peripheral Y(1) and Y(2) receptor antagonism in males, and Y(2) antagonism in females, corticosterone was significantly elevated. CONCLUSIONS AND IMPLICATIONS: NPY possesses a role in the gender-dependent susceptibility to stress-induced GI responses. Furthermore, NPY inhibits GI motility through Y(2) receptors and corticosterone release via peripheral Y(1) and Y(2) receptors.