C-FOS EXPRESSION IN SPECIFIC RAT-BRAIN NUCLEI AFTER INTESTINAL ANAPHYLAXIS - INVOLVEMENT OF 5-HT3 RECEPTORS AND VAGAL AFFERENT-FIBERS

The c-fos immediate-early gene is acutely induced in brain after various stimuli from the digestive tract. 5-HT3 receptors and vagal afferents have been found involved in intestinal motor disturbances induced by intestinal anaphylaxis. Our aim was to determine whether intestinal anaphylaxis activates brain structures, using c-fos expression, and to evaluate the modulation of c-fos induction by 5-HT3 receptors and vagal afferents. The effects of antigen challenge on intestinal motility were evaluated in ovalbumin-sensitized Hooded Lister rats chronically fitted with NiCr electrodes in the jejunal wall. Intestinal motility was assessed in conscious rats pretreated or not by perivagal capsaicin or a 5-HT3 antagonist (ondansetron). In sensitized rats, ovalbumin disrupted for 62.4 +/- 9.5 min the jejunal migrating motor complexes (MMC) and an important c-fos expression was detected in the nucleus tractus solitarius (NTS), lateral parabrachial nucleus (LPB) and paraventricular nucleus of the hypothalamus (PVN). Intraperitoneal administration of ondansetron or perivagal capsaicin treatment significantly reduced the duration of MMC disruption and attenuated markedly c-fos staining in the 3 brain sites. In contrast, intracerebroventricular administration of ondansetron significantly reduced jejunal motor alterations but did not diminish the c-fos expression, suggesting a role of central 5-HT3 receptors in the efferent control of the intestinal disturbances. Blockade of both c-fos expression and MMC disruption by systemic ondansetron and by perivagal capsaicin indicates that some brainstem nuclei are involved in digestive disturbances after intestinal anaphylaxis, and reflects an involvement of peripheral 5-HT3 receptors on vagal afferents. The reduction of c-fos staining in NTS as well as in LPB and PVN after perivagal capsaicin suggests that the NTS is the primary relay in the activation of the central nervous system during intestinal allergic challenge.