| The stress response is a complex biochemical cascade, including the release of diverse chemicals (for example, catecholamines, opiates, glucocorticoids) that can affect various aspects of brain structures and physiological processe (memory). Memory can be especially damaged by stress. Thus, to investigate the one of stress factors can be well provided valuable insights into the mnemonic process.The hippocampus is the most important structural foundation of the memory processing and storage. This hippocampus is also a target of stress hormones, having one of the highest concentrations of receptors for corticosteroids in the mammalian brain. Study suggests that stress caused several transient and permanent changes in the hippocampus. These stress-associated changes in the brain can influence learning-and-memory processes.In addition, the endogenous opioid system plays an important role in the memory processes and storage. The endogenous opioid system consists of three receptors, mu, delta, and kappa. The mu receptor has been a widely concern for regulating memory. Previous study suggests that injections of β-FNA into the CA3 region, but not into intracerebroventricular, caused a significant impairment in the spatial learning, and pre-training morphine impairs spatial memory acquisition. Meanwhile, the stress reaction also involves the endogenous opioid system. The level of endogenous opioid petides, glucocorticoid (CORT) and the pituitary hormone have a close relationship in the stress reaction. Stress factor is one of the main reasons for endogenous opioid system activation in brain. Therefore, it is valuble to make sure whether mu-opioid receptor participates in the process of learning and memory’ impairment by stress.Long-term changes of synaptic transmission in memory-related brain regions are considered to be the molecular basis of learning and memory. Here we investigated the effects of acute elevated platform (EP) stress on long-term potentiation (LTP) induction in CA1 region of the hippocampus of anesthetized mice, and the modulation of mu receptors on LTP induction of stressed mice. In vivo field excitatory postsynaptic potentials (fEPSPs) induced by electric stimulating Shaffer fiber in CA1 was recorded to evaluate the change on glutamaergic synaptic transmission. The change of the fEPSPs slope was analyzed. The main results are as follows.(1) EP stress inhibits long-term potentiation (LTP) induced by high frequency stimulation (HFS)In control group, LTP was induced successfully by HFS. But in stress group, LTP induction was failed. These results indicated that stress inhibits LTP induction.(2) EP stress inhibits LTP by activating the glucocorticoid receptorSystemic application of RU-486, a glucocorticoid receptor antagonist, rescued LTP in stressed mice, indicating that EP stress can inhibit LTP by activating the glucocorticoid receptor.(3) Systemic application of CORT mimics the effect of EP stress on LTPSimilar to EP stress, intraperitoneal injection of CORT (1 mg/kg) 30 min prior to HFS induction inhibited LTP expression.(4) LTP also could be inhibited by activating the mu-opioid receptorIn DAMGO group, LTP can not be induced after HFS that compared with basic fEPSPs. These results indicated that LTP has been inhibited by activating the mu-opioid receptor.(5) Mu-opioid receptor is involved in LTP inhibition induced by EP stress.In Nal+CORT group, compared with basic fEPSPs, LTP can be induced after HFS. The results demonstrated that LTP can be induced by suppressed mu-opioid receptor in the activation of the glucocorticoid receptor’s mice after HFS.In conclusion, we found that EP stress inhibits LTP by activating the glucocorticoid receptor and in which mu-opioid receptor plays an important role. The activation of mu-opioid receptor is likely to regulate the process of learning and memory’ impairment that induced by stress. |
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