Central Oxytocin is Involved in Mediating the Adaptation Mechanism of Colonic Transit Following Chronic Homotypic Stress in Rats

Abstract

Background: Central oxytocin has anti-stress effects via inhibiting the gene expression of corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN).We have previously shown that accelerated colonic transit in response to acute restraint stress was no longer observed following 5 consecutive days of restraint stress loading (chronic homotypic stress) (Neurosci Lett 453, 147-150, 2009). Our recent study showed that central oxytocin is involved in mediating restored gastric emptying following chronic homotypic stress in rats (Am J Physiol 299, G946-53, 2010). We studied whether central oxytocin is involved in mediating the adaptation mechanism of colonic transit following chronic homotypic and heterotypic stress in rats. Methods: A catheter was inserted into the proximal colon to measure colonic transit. A cannula was implanted into the right lateral ventricle for intracerebroventricular (icv) access. Five days after the surgery, the rats were exposed to chronic homotypic stress or heterotypic stress. For chronic homotypic stress, the rats were given restraint stress for 90 min for 5 consecutive days. For chronic heterotypic stress, the rats were given different types of stress (water avoidance stress, force swimming stress, cold restraint stress, and restraint stress) for 7 consecutive days. Ninety min after the injection of 51Cr (0.2 μCi) into the proximal colon on the 5th or 7th day of chronic stress, the entire colon was removed to measure geometric center (GC; the distribution of 51Cr). Oxytocin (0.5 μg), oxytocin receptor antagonists {[d(CH2)5,Try(Me),Orn]-oxytocin}(100 ng), CRF1 receptor antagonists (NBI-27914; 100 μg) and CRF2 receptor antagonists (astressin2-B; 10 μg) were administered (icv) 30 min before the stress loading. Saline-injected rats served as controls. Expression of oxytocin and CRF mRNA in the PVN was evaluated by in situ hybridization. Results: Colonic transit was no longer accelerated following chronic homotypic stress (GC; 5.8 ± 0.2, n=7), which was antagonized by icv-injection of oxytocin antagonists (GC; 7.9 ± 0.1, n=6, P<0.05). The increased oxytocin and decreased CRF mRNA expression at the PVNwere observed following chronic homotypic stress. In contrast, chronic heterotypic stress significantly accelerated colonic transit (GC; 8.6 ± 0.2; n=7, P<0.01). Accelerated colonic transit following chronic heterotypic stress was attenuated by icv-injection of oxytocin (GC; 6.7 ± 0.2, n=7, P<0.05) and NBI-27914 (GC; 6.42 ± 0.1; n=7), but not astressin2-B (GC; 8.0 ± 0.2, n=7). Oxytocin mRNA expression was no longer increased following chronic heterotypic stress. Conclusion: It is suggested that central oxytocin plays a pivotal role in mediating the adaptation mechanism of colonic transit following chronic homotypic, but not heterotypic, stress in rats.