NMDA Essential Receptor Expression And Nitric Oxide Production In Rat Brain After Chronic Mild Stress

BackgroundMajor depression is a common, severe and chronic psychiatric disorder with high rates of prevalence and relapse, suicide is also very common; it represents heavy burden of disease on society and is considered a significant public health concern. Though available antidepressant medications may be efficacious in most patients, there is a delayed onset in relief of symptoms and a larger number of individuals fail to respond or only partial respond to treatment. Furthermore, among available antidepressants, selective serotonin reuptake inhibitors and enhancer tianeptine both play a positive role in medication. In the light of the above clinical paradox, which is difficult to be explained by monoamine hypothesis, numerous studies are conducted on different animal models of depression indicating psychobiology and psychopharmacology. As we all know, stress contributes to depression, thus stress related animal models are quite universal in researches on depression and antidepressants. More and more evidence indicated that depression is a complex disorder; its mechanism may be related to many neurotransmitter systems in the brain.Thus the radical reason and last pathway of antidepressant medication is also unknown.Glutamate is the most important excitory neurotransmitter. Numerous studies indicate that glutamate N-Methyl-D-Aspartate (NMDA) receptor contributes to excitatory synaptic transduction, neuroplasticity, brain development, learning and memory as well. Recent researches indicated that glutamatergic dysfunction also participate in the pathophysiology of some neuro- and psycho-diseases such as cerebral vascular disease, trauma, epilepsy and schizophrenia. Few literatures is related to anxiety and depression disorder. Evidence indicates that some antidepressant drugs interact directly with NMDA receptor complex and nitric oxide synthesis activity in vitro. In addition, several NMDA receptor antagonists or nitric oxide synthesis inhibitor show a neuroproctive role and have beneficial effects on relieving depression symptoms. While relation between NMDA essential receptor expression and depression rat of chronic mild stress has not yet been performed.ObjectiveThe first purpose of the present study was to establish an animal model of depression; single raise and chronic mild stress were combined in this model. On the basis of depression model, study was designed to determine whether nitric oxide production and NMDA essential receptor expression level changed within prefrontal cortex and hippocampus in chronic mild stress rat brain. Results may also be helpful to explore mechanism of depression and develop newer generation antidepressant.MethodsAfter seven days accommodation, sixteen adult male Sprague-Dawley rats were allocated into control group and model group randomly; model rats were exposed to a variety of mild stressors sequentially, which include period changes of environment, light/dark rhythm, deprivation of food or water etc. Weight gain, open field test andsucrose solution consumption were investigated before and after procedure; spectrophotometric assays and immunoblot techniques were employed to determine nitric oxide production and NMDA essential receptor expression changed within rat prefrontal cortex and hippocampus.Results1. Over eighteen days mild stress, rats showed decreased locomotion, loss of interest, anhedonia and less weight gain which simulated clinical depressive features. At the endpoint of stress, model group had less weight gain (80.75卤13.38) g than control group (128.19+18.22) g, and less spontaneous locomotor activity (22.62卤12.26 vs 43.75119.88) in open field test, these differences between the two groups reach statistical significant. There is no significance in absolute sucrose assumption before and after stress (/M).060). While relative sucrose assumption (absolute value/weight) is lesser after stress (0.28卤0.03 vs 0.19 0.04, /MX001).2. Nitric oxide production increased in both prefrontal cortex and hippocampus aft...