Chronic Stress On Gastric Motility And Its Relationship With The Hippocampal Glu Receptor

Depression, a kind of mental disease, is closely related to stress, and the major character of it is significant-lasting depressed feeling or mood. Although the core symptom of depression is anhedonia, inability to experience pleasure , depression accompanys the dysfunction of autonomic nervous system, such as the changes of weight (decrease or increase) and the down-regulation of autonomic movement. Functional gastrointestinal disorder (FGlDs), which is a kind of digestive disease, is not explained with organic lesion or abnormal biochemical indicators. With the setting up of biological-psychology-social, it is recognized that the onset and development of functional gastrointestinal disorder (FGIDs) is associated with various mental factors, such as depression, anxiety. However, the current researches on depression played more attention to behavior and the activities of gastrointestinal got less attention. Hippocampus, belonging to the forebrain cortex, plays an important role in regulating emotional reaction and gastrointestinal activities. Some recent studies show the levels of hippocampal Glu significantly higher than the value of basic when received chronic stress, simultaneously, pharmacological studies suggest that the traditional monoamine neurotransmitter dysfunction hypothesis cannot perfect explain the pathogenesis of depression. Therefore, the hippocampal NMDAR and AMPAR, which are Glu receptors, are given greater attention in depression researches at present, but the exceedingly activated NMDA receptor and AMPA receptor can evoke an opposite effect of intracellular events: NMDA receptor is excessively activated to cause intracellular Ca²⁺ overload, which lead to cell damage; activating AMPA receptor can increase brain-derived neurotrophic factor (BDNF) expression. NMDA receptor antagonists show antidepressant-like effect, however a recent study shows AMPA receptor antagonist NBQX can attenuate the reduction in immobility time ketamine(NMD receptor antagonist)-induced during stress. But they are unknown that the role of NMDA receptor and AMPA receptor in stress-induced changes of gastric activities and the relationship of this two receptor. It is unknown whether intro-hippocampal injection of excessive dose of Glu can cause depression and the change of gastrointestinal activity, furthermore, the role of NMDAR and AMPAR in stress-induced changes of gastric activities and the relationships between this two types of glutamate receptors in regulating gastric activities is still not reported. The main goal in this experiment is to investigate the effect of CUMS on gastric activity, the role of hippocampal Glu, AMPAR and NMDAR in CUMS-induced gastric activity changes and the relationships between AMPAR and NMDAR via using the CUMS model, stereotaxic and intra-hippocampal microinjection, monitoring the rats behaviors and recording gastric mobility. Behaviors were monitored by the changes in body weight, the sucrose preference-test, the open field-test (OFT) and the forced swimming-test (FST). Intragastric pressure and gastric mobility were recorded on Powerlab/8sp. The result are: (1)Compared with the control, 21-day CUMS significantly reduced the increasing amplitude in body weight(p<0.05), the sucrose preference(p<0.01), and locomotion in OFT(p<0.01), but markedly prolonged the duration of immobility time in FST(p<0.01). Meanwhile, the average intragastric pressure and the magnitudes of gastric contraction were significantly declined(p<0.01)after 21 days CUMS. (2)Microinjection of Glu into hippocampus mimics the behaviors which were produced in CUMS. The down-rang of gastric mobility in the group of Glu injection was smaller than CUMS, but was much larger than the control. (3)Intrahippocampal microinjection of MK-801 ameliorated depression-like behaviors induced by CUMS(p<0.01), and attenuated stress-induced inhibition of intragastric pressure(p< 0.01). Wlntra-hippocampal injection of NBQX 10min before injecting MK-801 during CUMS significantly low the sucrose preference, the increasing amplitude in body weight, locomotion in OFT compared(p<0.05); markedly prolonged the duration of immobility time in FST(p<0.01); significantly weakened gastric activity(p<0.05) with MK-801+CUMS group. Simultaneously, there was no significant difference between "NBQX+MK-801+CUMS" group and CUMS group in behavior and gastro mobility(p>0.05).Conclusion: (1)21-day CUMS and hippocampal microinjection of Glu can cause the rat depression-like behaviors, meanwhile it can also inhibit gastric activity. (2)Hippocampal Glu cause the rat depression-like behaviors and weakened gastric activity by excessively activating NMDA receptor. Indigestion caused by weak gastro mobility may be one of the symptoms of depression. (3)Hippocampal AMPA receptor and NMDA receptor is not only involved in the onset of CUMS-induced depression-like behaviors, but also involved in the changes in gastric activity caused by CUMS-induced depression. Moreover, it is through activating AMPA receptor or adding AMPA receptor that MK-801 exerted rapid antidepressant effects and weakened stress-induced inhibition of gastric activity.