Central Neuropeptide y Plays an Important Role in Mediating the Adaptation Mechanism Against Chronic Stress in Male Rats

Abstract

Exposure to continuous life stress often causes gastrointestinal (GI) symptoms. Studies have shown that neuropeptide Y (NPY) counteracts the biological actions of corticotrophin-releasing factor (CRF) and is involved in the termination of the stress response. However, in chronic repeated restraint stress (CRS) conditions, the actions of NPY on GI motility remain controversial. To evaluate the role of NPY in mediation of the adaptation mechanism and GI motility in CRS conditions, a CRS rat model was set up. Central CRF and NPY expression levels were analyzed, serum corticosterone and NPY concentrations were measured, and GI motor function was evaluated. The NPY Y1 receptor antagonist BIBP-3226 was centrally administered before stress loading, and on days 1 through 5 of repeated stress, the central CRF and the serum corticosterone concentrations were measured. In addition, gastric and colonic motor functions were evaluated. The elevated central CRF expression and corticosterone concentration caused by acute stress began to fall after 3 days of stress loading, whereas central NPY expression and serum NPY began to increase. GI dysmotility also returned to a normal level. Pretreatment with BIBP-3226 abolished the adaptation mechanism and significantly increased CRF expression and the corticosterone concentration, which resulted in delayed gastric emptying and accelerated fecal pellet output. Inhibited gastric motility and enhanced distal colonic motility were also recorded. CRS-produced adaptation, overexpressed central CRF, and GI dysmotility observed in acute restraint stress were restored to normal levels. Central NPY via the Y1 receptor plays an important role in mediating the adaptation mechanism against chronic stress.