Irritable bowel syndrome (IBS) is a common disorder mainly characterized by altered bowel habits and visceral pain. In this study, we investigated the role of tachykinin NK 1 receptors in the visceral pain response (abdominal muscle contraction) caused by colorectal distention in rabbits previously subjected to colonic irritation, using the selective tachykinin NK 1 receptor antagonists TAK-637 [(aR,9R)-7-[3,5-Bis(trifluoromethyl)benzyl]-8,9,10,11-tetrahydro-9-methyl-5-Intracolorectal administration of 0.8% acetic acid solution enhanced the nociceptive response to colorectal distention, producing a significant increase in the number of abdominal muscle contractions. Under these conditions, intraduodenal TAK-637 (0.1-3 mg/kg) dose dependently decreased the number of distention-induced abdominal contractions, and a significant inhibitory effect was observed with doses of 0.3 to 3 mg/kg. Another tachykinin NK 1 antagonist, (Ϯ)-CP-99,994, also reduced the number of abdominal contractions. In contrast, the enantiomer of TAK-637 (which has very weak tachykinin NK 1 receptor antagonistic activity), trimebutine maleate, ondansetron, and atropine sulfate did not inhibit the abdominal response. The main metabolite of TAK-637, which has more potent tachykinin NK 1 receptor antagonistic activity but permeates the central nervous system less well than TAK-637, produced less inhibition of the viscerosensory response. When given intrathecally, TAK-637 and (Ϯ)-CP-99,994 markedly reduced the number of abdominal contractions. These results suggest that tachykinin NK 1 receptors play an important role in mediating visceral pain and that TAK-637 inhibits the viscerosensory response to colorectal distention by antagonizing tachykinin NK 1 receptors, mainly in the spinal cord. They also suggest that TAK-637 may be useful in treating functional bowel disorders such as IBS.

Abstract. Stress-induced colonic functional changes have been investigated mainly under conditions involving physical stress, like in the restraint stress model. In this study, we established a new stress-induced defecation model involving the placement of Mongolian gerbils in a novel environment (novelty stress) and determined the effects of several drugs on novelty stress-induced fecal pellet output. When animals kept in groups were placed individually in small cages, the fecal pellet output markedly increased, although the upper intestinal transit measured by charcoal method was not changed. The concentration of plasma adrenocorticotropic hormone was moderately but significantly increased by the novelty stress. Drugs reportedly effective for stress-induced defecation, like alosetron hydrochloride, atropine sulfate, and trimebutine maleate, inhibited both the novelty stress-induced increase in fecal pellet output and spontaneous defecation. In contrast, TAK-637, a tachykinin NK 1 -receptor antagonist, and diazepam inhibited the novelty stress induced defecation but did not inhibit spontaneous defecation. The present study indicated that novelty stress increases fecal pellet output without affecting the upper intestinal transit; this model may be useful for evaluating the effects of drugs on stress-stimulated colonic motility.

The effects of neonatal asphyxia on the serotonin neuron system were examined using the immunoperoxidase method. Male mice, 2 days of age, were exposed to total asphyxia (100% C0₂) for 30 min. Mice that spontaneously survived were perfused transcardially with a fixative at 15, 30 and 60 days of age. Quantitative immunohistochemical analysis at 60 days of age demonstrated a significant decrease in the numbers of serotonin-immunoreactive cell bodies in the nucleus raphe dorsalis, the nucleus raphe pontis, the sub-pyramidal region, the total raphe system and the whole brain, while no significant reduction in the number of serotonin-immunoreactive cell bodies was observed in the caudal raphe system. Presumably degenerative changes in serotonin-immunoreactive fibers were observed in various parts of the brain of mice subjected to total asphyxia at 15 days of age, and the numbers of degenerated fibers decreased in almost all parts of the brain, the exception being the caudal portion of the brainstem, at 30 and 60 days of age. These results suggested that neonatal asphyxia induced permanent changes in the serotonin neuron system, with regional differences.

This investigation aimed to validate a Japanese version of the Modest Behavior Scale (MBS-J) to measure the behavioral aspects of modesty as a self-presentation tactic. Two preliminary surveys and three studies were conducted. Study 1 examined the factorial validity, construct validity, and internal consistency of the MBS, adding emic items generated from the Japanese sample in the preliminary surveys. The results confirmed a three-factor structure of Self-Effacement, Other-Enhancement, and Avoidance of Attention-Seeking, with good internal consistency for each subscale. Studies 1 and 3 also evinced appropriate correlations between the MBS-J subscales and theoretically related constructs, namely, trait modesty, independent and interdependent self-construal, self-efficacy, self-esteem, approval motivation, and dialectical self, suggesting good construct validity. Using a two-wave survey, Study 2 showed good test–retest reliability for the MBS-J. In Study 3, it was hypothesized that those with higher Self-Effacement tend to report lower explicit self-esteem owing to a self-presentation strategy instead of actual lower self-regard. The results showed that Self-Effacement was strongly negatively correlated with explicit self-esteem but not correlated with implicit self-esteem, supporting the hypothesis. These findings confirm the construct validity of this scale for modest behavior performed as self-presentation.

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