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Inhibitory effect of central oxytocin on acceleration of colonic motility induced by water-avoidance stress in rats
Abstracts / Neuroscience Research 68S (2010) e335–e446
P3-j28 Expression analyses of stress-related factors in single prolonged stress rats Takashi Hashimoto 1,2 , Ken-ichi Matsuda 1 , Mitsuhiro Kawata 1 1
Kyoto Pref. University of Med., Kyoto, Japan 2 JSPS, Tokyo, Japan
Post-traumatic stress disorder (PTSD) is a stress-related anxiety syndrome that develops after exposure to traumatic experience. It exhibits three major types of characteristic symptoms: flashback, avoidance, and hyperarousal, and many indivisuals with PTSD remain chronically symptomatic, implying that sustained structural and functional changes in brain is predisposing factors of PTSD. However, until today, biological basis of PTSD is almost unknown. Single prolonged stress (SPS) is an established animal model proposed for PTSD, and mimic the phathophysiological and behavioral characteristics of PTSD. In this study, by using SPS paradigm, we investigated the expressions of stress-related genes and proteins including corticotropinreleasing hormone (CRH), glucocorticoid receptor (GR), and brain-derived neurotrophic factor (BDNF) in the brain of adult male rats. Sprague–Dawley rats at 8 weeks, were subjected to a single session of prolonged stress consisting of immobilization, forced swimming, and exposure to ether vapor. Seven days after SPS treatment, expression of CRH, GR, BDNF mRNAs were measured by quantitative real-time PCR. CRH mRNA showed significant increase in the central nucleus of the amygdala in SPS rats. In SPS rats, we observed significant reduction of GR,and BDNF mRNAs in the dentate gyrus (DG) of hippocampal formation, and immunohistochemical staining also showed significant decrease of BDNF protein in the DG. These results suggest that SPS paradigm alters various stress-related factors in mammalian brains, and may provide the physiological and behavioral basis of PTSD. doi:10.1016/j.neures.2010.07.1750
P3-k01 Inhibitory effect of central oxytocin on acceleration of colonic motility induced by water-avoidance stress in rats Masahiro Matsunaga 1 , Masashi Yoneda 2 , Kunio Hideki Ohira 3 , Hirohito Tsuboi 1 , Hiroshi Kaneko 1 1
Kasugai 2 ,
Fujita Health University 2 Aichi Medical University 3 Nagoya University
Recent studies have indicated that brain and gut activities are interrelated and exposure to several stressors, such as water-avoidance stress, stimulates the motor function of the gut through corticotropin-releasing factor (CRF)-signaling pathways in the brain. Central oxytocin is known to attenuate stress responses, including CRF expression in the brain. In this study, we examined whether central oxytocin attenuated the acceleration of colonic motility induced by water-avoidance stress. Centrally administered oxytocin inhibited the accelerated colonic motility induced by water-avoidance stress. The effective dose ranged between 5 and 50 pmol on i.c.v. injection. Oxytocin also decreased the number of CRF-positive cells in the paraventricular nucleus and corticosterone release. The inhibitory effect of oxytocin on accelerated colonic motility was blocked by pretreatment with oxytocin receptor antagonist. Furthermore, centrally administered tocinoic acid enhanced the acceleration of colonic motility. These results suggested that endogenous central oxytocin may contribute to the regulation of colonic function and inhibit the brain CRF-signaling pathways targeting the gut, resulting in the inhibition of stress-induced colonic contractions. doi:10.1016/j.neures.2010.07.1751
P3-k02 Effects of prenatal exposure to titanium dioxide on activation of corticotrophin-releasing hormone neurons in mice Shinya Yanagita , Jiro Numazaki, Ken Takeda
Kanemaru, Masakazu
Umezawa, Rie
Facul Pharma Sci, Tokyo University of Science, Chiba Recent studies have indicated that exposure to Titanium dioxide (TiO2 ) induces deleterious effects, such as cytotoxicity and inflammatory response, in the CNS of rodents. We previously reported that prenatal exposure to TiO2 alters gene expressions related to brain development using microarray analysis. It is well known that developmental impairment of brain is in part attributed to dysfunction of HPA axis in both mother and offspring. Taken together, prenatal exposure to TiO2 may influence the activity of HPA axis during pregnant or postnatal periods. In this study, we examined the effects of prenatal exposure to TiO2 on activation of corticotrophin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN), which are one of the central activators of the integrated HPA axis using
e395
immunohistochemistry. In addition, we also examine the reactivity of CRH neurons in the PVN to stress stimuli in prenatal TiO2 exposed rats. TiO2 suspension or vehicle was injected subcutaneously to pregnant rats on the gestational day 6, 9, 12, 15, and 18 (0.1 mg per once, total 0.5 mg). 6weeks offspring rats were divided into 4 groups (i.e. vehicle-control, vehicle-stress, TiO2 -control, TiO2 -stress). The rats in stress group were received electrical stress (0.1 mA, for 10 s 2 times, interval 1 min) in the chamber. The rats in control group were kept sedentary, and were not received any stressful stimuli in the same chamber. A significant main effect for groups (control or stress) was observed in two-way ANOVA for the number of double Fos/CRH-positive neurons (p < 0.05). However, there was no significant main effect for TiO2 exposure on the activation of CRH neurons in the PVN. These results indicate that prenatal exposure to TiO2 did not induce remarkable response on the activation of CRH neurons, and suggests that TiO2 may not be potential stressor activating HPA axis of offspring at least in prenatal exposure. doi:10.1016/j.neures.2010.07.1752
P3-k03 Effects of Rikkunshito on the restraint stressinduced anorexia in rats Takashi Mera 1 , Sota Hayashida 1 , Masatoshi Takakazu Oka 2 , Sadatoshi Tsuji 1
Takahashi 1 ,
1 Division of Psychosomatic Medicine, Department of Neurology, School of medicie, University of Occupational and Environmental Health, Japan 2 Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University
Rikkunshito (Liu-Jun-Zi-Tang in Chinese) is a traditional herbal medicine, which is widely used for patients with chronic hypo-function of the gastrointestinal tract, including gastric flatulence, anorexia, nausea, and vomiting. Previous studies have demonstrated that Rikkunshito has an enhancing effect on gastric emptying, suppresses cisplatin-induced anorexia, and increases plasma ghrelin level via 5-HT2 receptor antagonism in rats. However, it is not known if Rikkunshito is effective for stress-induced anorexia. We therefore examined the effect of Rikkunshito on the restraint stress (RTS)induced anorexia in rats. Rats were randomly divided into two groups: RTS group and control group. Rats in each group were administered orally with Rikkunshito (1000 mg/kg body weight in distilled water) or vehicle (distilled water) at 17:00 h. After administration of Rikkunshito or vehicle, rats in RTS-group were restrained in plastic tubes (Broome Style Restrainers, PLAS LABS, Inc.) for 120 min. Control rats were kept in their home cages without any treatment for 120 min. Then, we measured their food intake (g) for 12 h (19:00–7:00 h) by using metabolism cage. Rats were housed individually in metabolism cages with free access to food and water in an air-conditioned room (24 ± 1 ◦ C) under a 12-h light (07:00–19:00 h)/12-h dark (19:00–07:00 h) cycle. In control group, there was no statistical significance in food intake between Rikkunshito-treated rats and vehicle-treated rats. The decrease of food intake caused by RTS was reversed significantly when Rikkunshito was administered. Rikkunshito may be effective for stressinduced anorexia, but not for normal food intake. doi:10.1016/j.neures.2010.07.1753
P3-k04 Chewing activates dopaminergic system to counteract stress-induced anxiety-like behavior Yumie Ono 1,2 Onozuka 1,2
, Megumi
Fukui 2 , So
Koizumi 2,3 , Minoru
1 Department Physiol and Neurosci, Kanagawa Dental College, Kanagawa, Japan 2 Res. Center of Brain and Oral Sci., Kanagawa Dent. Col., Kanagawa, Japan 3 Department Ortho, Kanagawa Dental College, Kanagawa, Japan
To determine how chewing affects the perception of stress, we studied anxiety-like behavior in rats that underwent exposure to stress with or without chewing. We subjected 10-week-old male Sprague-Dawley rats to immobilization stress for 30 min. We left half of them alone for the entire period (stressed group; ST). The other half were allowed to chew a wooden stick during immobilization (stressed and chewing group; SC). A control group of rats were left in individual cages for the same time period without any treatment. One hour after the end of the stress period (or control period), all rats were tested in the elevated plus maze. Some were intraperitoneally administrated D1-dopamine receptor antagonist SCH23390 (0.3 mg/kg) immediately before immobilization. Using in vivo microdialysis, we also measured extracellular concentrations of noradrenaline, dopamine, and serotonin in the ventral hippocampus, the brain region that generates anxiety-like behavior, of rats in both groups ST and
P3-j28 Expression analyses of stress-related factors in single prolonged stress rats Takashi Hashimoto 1,2 , Ken-ichi Matsuda 1 , Mitsuhiro Kawata 1 1
Kyoto Pref. University of Med., Kyoto, Japan 2 JSPS, Tokyo, Japan
Post-traumatic stress disorder (PTSD) is a stress-related anxiety syndrome that develops after exposure to traumatic experience. It exhibits three major types of characteristic symptoms: flashback, avoidance, and hyperarousal, and many indivisuals with PTSD remain chronically symptomatic, implying that sustained structural and functional changes in brain is predisposing factors of PTSD. However, until today, biological basis of PTSD is almost unknown. Single prolonged stress (SPS) is an established animal model proposed for PTSD, and mimic the phathophysiological and behavioral characteristics of PTSD. In this study, by using SPS paradigm, we investigated the expressions of stress-related genes and proteins including corticotropinreleasing hormone (CRH), glucocorticoid receptor (GR), and brain-derived neurotrophic factor (BDNF) in the brain of adult male rats. Sprague–Dawley rats at 8 weeks, were subjected to a single session of prolonged stress consisting of immobilization, forced swimming, and exposure to ether vapor. Seven days after SPS treatment, expression of CRH, GR, BDNF mRNAs were measured by quantitative real-time PCR. CRH mRNA showed significant increase in the central nucleus of the amygdala in SPS rats. In SPS rats, we observed significant reduction of GR,and BDNF mRNAs in the dentate gyrus (DG) of hippocampal formation, and immunohistochemical staining also showed significant decrease of BDNF protein in the DG. These results suggest that SPS paradigm alters various stress-related factors in mammalian brains, and may provide the physiological and behavioral basis of PTSD. doi:10.1016/j.neures.2010.07.1750
P3-k01 Inhibitory effect of central oxytocin on acceleration of colonic motility induced by water-avoidance stress in rats Masahiro Matsunaga 1 , Masashi Yoneda 2 , Kunio Hideki Ohira 3 , Hirohito Tsuboi 1 , Hiroshi Kaneko 1 1
Kasugai 2 ,
Fujita Health University 2 Aichi Medical University 3 Nagoya University
Recent studies have indicated that brain and gut activities are interrelated and exposure to several stressors, such as water-avoidance stress, stimulates the motor function of the gut through corticotropin-releasing factor (CRF)-signaling pathways in the brain. Central oxytocin is known to attenuate stress responses, including CRF expression in the brain. In this study, we examined whether central oxytocin attenuated the acceleration of colonic motility induced by water-avoidance stress. Centrally administered oxytocin inhibited the accelerated colonic motility induced by water-avoidance stress. The effective dose ranged between 5 and 50 pmol on i.c.v. injection. Oxytocin also decreased the number of CRF-positive cells in the paraventricular nucleus and corticosterone release. The inhibitory effect of oxytocin on accelerated colonic motility was blocked by pretreatment with oxytocin receptor antagonist. Furthermore, centrally administered tocinoic acid enhanced the acceleration of colonic motility. These results suggested that endogenous central oxytocin may contribute to the regulation of colonic function and inhibit the brain CRF-signaling pathways targeting the gut, resulting in the inhibition of stress-induced colonic contractions. doi:10.1016/j.neures.2010.07.1751
P3-k02 Effects of prenatal exposure to titanium dioxide on activation of corticotrophin-releasing hormone neurons in mice Shinya Yanagita , Jiro Numazaki, Ken Takeda
Kanemaru, Masakazu
Umezawa, Rie
Facul Pharma Sci, Tokyo University of Science, Chiba Recent studies have indicated that exposure to Titanium dioxide (TiO2 ) induces deleterious effects, such as cytotoxicity and inflammatory response, in the CNS of rodents. We previously reported that prenatal exposure to TiO2 alters gene expressions related to brain development using microarray analysis. It is well known that developmental impairment of brain is in part attributed to dysfunction of HPA axis in both mother and offspring. Taken together, prenatal exposure to TiO2 may influence the activity of HPA axis during pregnant or postnatal periods. In this study, we examined the effects of prenatal exposure to TiO2 on activation of corticotrophin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN), which are one of the central activators of the integrated HPA axis using
e395
immunohistochemistry. In addition, we also examine the reactivity of CRH neurons in the PVN to stress stimuli in prenatal TiO2 exposed rats. TiO2 suspension or vehicle was injected subcutaneously to pregnant rats on the gestational day 6, 9, 12, 15, and 18 (0.1 mg per once, total 0.5 mg). 6weeks offspring rats were divided into 4 groups (i.e. vehicle-control, vehicle-stress, TiO2 -control, TiO2 -stress). The rats in stress group were received electrical stress (0.1 mA, for 10 s 2 times, interval 1 min) in the chamber. The rats in control group were kept sedentary, and were not received any stressful stimuli in the same chamber. A significant main effect for groups (control or stress) was observed in two-way ANOVA for the number of double Fos/CRH-positive neurons (p < 0.05). However, there was no significant main effect for TiO2 exposure on the activation of CRH neurons in the PVN. These results indicate that prenatal exposure to TiO2 did not induce remarkable response on the activation of CRH neurons, and suggests that TiO2 may not be potential stressor activating HPA axis of offspring at least in prenatal exposure. doi:10.1016/j.neures.2010.07.1752
P3-k03 Effects of Rikkunshito on the restraint stressinduced anorexia in rats Takashi Mera 1 , Sota Hayashida 1 , Masatoshi Takakazu Oka 2 , Sadatoshi Tsuji 1
Takahashi 1 ,
1 Division of Psychosomatic Medicine, Department of Neurology, School of medicie, University of Occupational and Environmental Health, Japan 2 Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University
Rikkunshito (Liu-Jun-Zi-Tang in Chinese) is a traditional herbal medicine, which is widely used for patients with chronic hypo-function of the gastrointestinal tract, including gastric flatulence, anorexia, nausea, and vomiting. Previous studies have demonstrated that Rikkunshito has an enhancing effect on gastric emptying, suppresses cisplatin-induced anorexia, and increases plasma ghrelin level via 5-HT2 receptor antagonism in rats. However, it is not known if Rikkunshito is effective for stress-induced anorexia. We therefore examined the effect of Rikkunshito on the restraint stress (RTS)induced anorexia in rats. Rats were randomly divided into two groups: RTS group and control group. Rats in each group were administered orally with Rikkunshito (1000 mg/kg body weight in distilled water) or vehicle (distilled water) at 17:00 h. After administration of Rikkunshito or vehicle, rats in RTS-group were restrained in plastic tubes (Broome Style Restrainers, PLAS LABS, Inc.) for 120 min. Control rats were kept in their home cages without any treatment for 120 min. Then, we measured their food intake (g) for 12 h (19:00–7:00 h) by using metabolism cage. Rats were housed individually in metabolism cages with free access to food and water in an air-conditioned room (24 ± 1 ◦ C) under a 12-h light (07:00–19:00 h)/12-h dark (19:00–07:00 h) cycle. In control group, there was no statistical significance in food intake between Rikkunshito-treated rats and vehicle-treated rats. The decrease of food intake caused by RTS was reversed significantly when Rikkunshito was administered. Rikkunshito may be effective for stressinduced anorexia, but not for normal food intake. doi:10.1016/j.neures.2010.07.1753
P3-k04 Chewing activates dopaminergic system to counteract stress-induced anxiety-like behavior Yumie Ono 1,2 Onozuka 1,2
, Megumi
Fukui 2 , So
Koizumi 2,3 , Minoru
1 Department Physiol and Neurosci, Kanagawa Dental College, Kanagawa, Japan 2 Res. Center of Brain and Oral Sci., Kanagawa Dent. Col., Kanagawa, Japan 3 Department Ortho, Kanagawa Dental College, Kanagawa, Japan
To determine how chewing affects the perception of stress, we studied anxiety-like behavior in rats that underwent exposure to stress with or without chewing. We subjected 10-week-old male Sprague-Dawley rats to immobilization stress for 30 min. We left half of them alone for the entire period (stressed group; ST). The other half were allowed to chew a wooden stick during immobilization (stressed and chewing group; SC). A control group of rats were left in individual cages for the same time period without any treatment. One hour after the end of the stress period (or control period), all rats were tested in the elevated plus maze. Some were intraperitoneally administrated D1-dopamine receptor antagonist SCH23390 (0.3 mg/kg) immediately before immobilization. Using in vivo microdialysis, we also measured extracellular concentrations of noradrenaline, dopamine, and serotonin in the ventral hippocampus, the brain region that generates anxiety-like behavior, of rats in both groups ST and