Sustained Delayed Gastric Emptying During Repeated Restraint Stress in Oxytocin Knockout Mice

Abstract

We have recently shown that impaired gastric motility observed in acute restraint stress was restored following repeated restraint stress in mice. Repeated restraint stress up-regulates oxytocin mRNA expression and down-regulates corticotrophin-releasing factor (CRF) mRNA expression at the hypothalamus. Oxytocin knockout mice (OXT-KO) have been widely used to study the central oxytocin signalling pathways in response to various stressors. We studied the effects of acute and repeated restraint stress on solid gastric emptying and hypothalamic CRF mRNA expression in wild-type (WT) and OXT-KO mice. Heterozygous (HZ) parents (B6; 129S-Oxt(tm1Wsy)/J mice) were bred in our animal facility. Male OXT-KO, WT and HZ littermates were used for the study. Solid gastric emptying was measured following acute restraint stress (for 90 min) or repeated restraint stress (for five consecutive days). Expression of CRF mRNA in the paraventricular nucleus (PVN) was measured by real-time reverse transcriptase-polymerase chain reaction. There were no significant differences of gastric emptying in WT (68.4 ± 4.1%, n = 6), HZ (71.8 ± 3.1%, n = 6) and OXT-KO (70.6 ± 3.1%, n = 6) mice in nonstressed conditions. Acute stress significantly delayed gastric emptying in OXT-KO mice (33.10 ± 2.5%, n = 6) WT (39.1 ± 1.1%, n = 6) and HZ mice (35.8 ± 1.2%, n = 6). Following repeated restraint stress loading, gastric emptying was significantly restored in WT (68.3 ± 4.5%, n = 6) and HZ mice (63.1 ± 2.6%, n = 6). By contrast, gastric emptying was still delayed in OXT-KO mice (34.7 ± 1.3%, n = 6) following repeated restraint stress. The increase in CRF mRNA expression at the PVN was much pronounced in OXT-KO mice compared to WT or HZ mice following repeated restraint stress. These findings suggest that central oxytocin plays a pivotal role in mediating the adaptation mechanism following repeated restraint stress in mice.