| 其他摘要 | Drug addiction is characterized by persistent and compulsive drug craving and re-lapses. Recent evidence indicates that the hippocampus plays crucial roles in the processes of drug craving and relapses triggered by drug-associated cues or stress. Epigenetic mechanisms play important roles in memory, stress and drug addiction. Methyl-CpG binding protein 2 (MeCP2) is highly expressed in the brain, especially the hippocampus. MeCP2 specifically recognize methylated DNA and the main function is to regulate gene transcription via the interaction with methylated DNA. MeCP2 can regulate activity-dependent gene expression. It also modulates synaptic structure and function, as well as learning and memory. So far, how Acute and chronic morphine treatments affect MeCP2 gene expression is not clear. In this study, we use qPCR (real-time quantitative PCR) technology to detect hippo-campal MeCP2 gene expression levels in different addictive stages. Firstly, this re-search focuses on hippocampal MeCP2 gene expression following acute morphine treatment, during the process of chronic morphine treatments and morphine with-drawal. We find that 1 hour after the acute morphine administration, MeCP2 gene expression in the mouse hippocampus is significantly up-regulated. However, MeCP2 mRNA levels are down-regulated by μ-opioid receptor agonist, naloxone. Accompanied by chronic morphine exposure, MeCP2 mRNA level shows an inverted "V" shape, suggesting that hippocampal MeCP2 is involved in morphine addcition. More importantly, withdrawal for 1 hour after chronic morphine treatment, the expression of MeCP2 gene in hippocampus is reduced sharply, which is just contrast to acute morphine group at the that time. Whereas, MeCP2 mRNA level is characterized by a persistent enhancement during morphine withdrawal. Secondly, stress is involved in regulating the expression of hippocampal MeCP2 gene after the administration of acute morphine, since RU38486, glucocorticoid receptor antagonist, can block the acute morphine-inducing the up-regulation of MeCP2, NR2A, NR2B, GluR1, GluR2 ,KCC2 and NSF. Finally, along with the establishment of morphine tolerance, hippocampal MeCP2 expression shows significant dynamic changes, which indicates that hippocampal MeCP2 may be involved in regulating morphine tolerance. These preliminary results lay the foundation for future research on intervention effect of MeCP2 on addiction, stress or environmental cues trigger drug seeking behavior and its mechanism of hippocampal synaptic plasticity. |
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