Increasing evidence has demonstrated that emotional states and intestinal conditions are inter-connected in so-called “brain–gut interactions.” Indeed, many psychiatric disorders are accompanied by ...gastrointestinal symptoms, such as the irritable bowel syndrome (IBS). However, the functional connection remains elusive, partly because there are few useful experimental animal models. Here, we focused on a highly validated animal model of stress-induced psychiatric disorders, such as depression, known as the chronic vicarious social defeat stress (cVSDS) model mice, which we prepared using exposure to repeated psychological stress, thereafter examining their intestinal conditions. In the charcoal meal test and the capsaicin-induced hyperalgesia test, cVSDS model mice showed a significantly higher intestinal transit ratio and increased visceral pain-related behaviors, respectively. These changes persisted over one month after the stress session. On the other hand, the pathological evaluations of the histological and inflammatory scores of naive and cVSDS model mice did not differ. Furthermore, keishikashakuyakuto—a kampo medicine clinically used for the treatment of IBS—normalized the intestinal motility change in cVSDS model mice. Our results indicate that cVSDS model mice present IBS-like symptoms such as chronic intestinal peristaltic changes and abdominal hyperalgesia without organic lesion. We therefore propose the cVSDS paradigm as a novel animal model of IBS with wide validity, elucidating the correlation between depressive states and intestinal abnormalities.
Recently, ultrasound exposure has been shown to be a noninvasive method for modulating brain activity and has to be applied to treat mental disorders, such as depression. However, its underlying ...mechanism remains unclear. Therefore, there is a need for animal models that can investigate the mechanism of ultrasound exposure. In this study, we utilized olfactory bulbectomized (OB) rats as an animal model of depression and investigated their emotional state following ultrasound exposure. As a result, following exposure to high-frequency ultrasonic vocalizations (USV)s of rats, the hyperemotionality of OB rats was significantly suppressed. Also, USV exposure significantly reduced the latency to the first entry into the open arm in the elevated plus maze tests and the plasma corticosterone levels of OB rats. Furthermore, artificial ultrasounds (50 and 100 kHz) also significantly decreased the hyperemotionality score of OB rats. These results suggested that ultrasound exposure, regardless of vocal or artificial sound, ameliorated depressive-like behavior and stress level in OB rats. We proposed that OB rats might be an appropriate animal model to identify mechanisms underlying the effects of ultrasound exposure.
Recently, we developed that the mice chronic vicarious social defeat stress (cVSDS) model, known as validated animal model of depression, showed the irritable bowel syndrome (IBS)-like symptoms such ...as chronic intestinal motility changes and abdominal hyperalgesia without organic lesions. Previously, we reported that a selective delta opioid receptor (DOP) agonist KNT-127 improved the depression-like behaviors observed in mice cVSDS model. In the present study, we examined the effects of KNT-127 on the IBS-like symptoms in cVSDS model. The model mice were prepared by exposure to repeated psychological stress for 10 days in C57BL/6J mice. KNT-127 was administered subcutaneously (s.c.) and microinjected into the Insular cortex (IC) 30min before the test, respectively. KNT-127 (10mg/kg, s.c.) significantly improved increased intestinal transit ratio in the charcoal meal test and hypersensitivity symptoms in the capsaicin-induced hyperalgesia test, respectively. In addition, KNT-127 (300ng/mouse) in IC was normalized their intestinal transit ratio. These results suggested that KNT-127 improved the IBS-like symptoms in cVSDS mice via DOPs in IC. We proposed that DOP agonist have the potential to be an effective treatment for IBS, capable of breaking the vicious cycle in gut-brain interactions.
Recently, we developed that the mice chronic vicarious social defeat stress (cVSDS) model, known as validated animal model of depression, showed the irritable bowel syndrome (IBS)-like symptoms such ...as chronic intestinal motility changes and abdominal hyperalgesia without organic lesions. Previously, we reported that a selective delta opioid receptor (DOP) agonist KNT-127 improved the depression-like behaviors observed in mice cVSDS model. In the present study, we examined the effects of KNT-127 on the IBS-like symptoms in cVSDS model. The model mice were prepared by exposure to repeated psychological stress for 10 days in C57BL/6J mice. KNT-127 was administered subcutaneously (s.c.) and microinjected into the Insular cortex (IC) 30min before the test, respectively. KNT-127 (10mg/kg, s.c.) significantly improved increased intestinal transit ratio in the charcoal meal test and hypersensitivity symptoms in the capsaicin-induced hyperalgesia test, respectively. In addition, KNT-127 (300ng/mouse) in IC was normalized their intestinal transit ratio. These results suggested that KNT-127 improved the IBS-like symptoms in cVSDS mice via DOPs in IC. We proposed that DOP agonist have the potential to be an effective treatment for IBS, capable of breaking the vicious cycle in gut-brain interactions.
Recently, ultrasound exposure has been shown to be a noninvasive method for modulating brain activity and has to be applied to treat mental disorders, such as depression. However, its underlying ...mechanism remains unclear. Therefore, there is a need for animal models that can investigate the mechanism of ultrasound exposure. In this study, we utilized olfactory bulbectomized (OB) rats as an animal model of depression and investigated their emotional state following ultrasound exposure. As a result, following exposure to high-frequency ultrasonic vocalizations (USV)s of rats, the hyperemotionality of OB rats was significantly suppressed. Also, USV exposure significantly reduced the latency to the first entry into the open arm in the elevated plus maze tests and the plasma corticosterone levels of OB rats. Furthermore, artificial ultrasounds (50 and 100 kHz) also significantly decreased the hyperemotionality score of OB rats. These results suggested that ultrasound exposure, regardless of vocal or artificial sound, ameliorated depressive-like behavior and stress level in OB rats. We proposed that OB rats might be an appropriate animal model to identify mechanisms underlying the effects of ultrasound exposure.