Tu1789 Brain Activation With Rectal Distention Distinguishes Irritable Bowel Syndrome From Healthy Controls and Is Independent of Psychiatric Comorbidity

Abstract

gastric motility in females is due to a higher GABAergic input to gastricprojecting DMV neurons. In an in vivo anesthetized preparation, microinjections of bicuculline methiodide (BIC, 0.5-50pmoles in 60 nl) into the DMV of Sprague-Dawley rats increased gastric tone in a dose-dependent manner. In males, microinjection of 0.5 pmoles of BIC elicited a 32.0±12 mg increase in gastric tone (N=2), whereas microinjection of 50 pmoles of BIC elicited an increase of 186.0±23 mg (N=2). In females, DMV microinjections of 0.5 pmoles of BIC elicited a significantly greater increase in gastric tone compared to males (200.5±37; N=3; p<0.05). Whole-cell patch-clamp recordings were made from identified gastric-projecting DMV neurons. Female rats displayed an increased afterhyperpolarization amplitude and decay time (19.7±2mV;180.7±39ms; N=12) compared tomales (15.9±1mV afterhyperpolarization amplitude; 103.9±24 ms decay time; N=9; p<0.05), and a lower action potential frequency response to injection of 80 pA of current (13.6±1 events/s in males; 9.2±1 events/ s in females). These differences are indicative of a decreased excitability of neurons in females. Females also had a higher frequency of miniature inhibitory postsynaptic currents compared to males (1.2±0.3, N=7, and 0.7±0.04, N=4, events/s in females and males, respectively). These data indicate that gastric-projecting DMV neurons in females are less excitable and receive a higher tonic GABAergic input compared to males. These data suggest that reduced gastric motility in females may be due to an increased inhibitory input to gastric-projecting neurons.