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首页> 外文期刊>Acta Pharmacologica Sinica >Changes of brain neuropeptide Y and its receptors in rats with flurazepam tolerance and dependence
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Changes of brain neuropeptide Y and its receptors in rats with flurazepam tolerance and dependence

机译:氟西epa耐受性和依赖性大鼠脑神经肽Y及其受体的变化

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Aim: Anticonvulsant tolerance and dependence are two obstacles that restrict the clinical use of benzodiazepines (BDZ). In order to explore the mechanism of these two adverse reactions, changes of neuropeptide Y (NPY) and its receptors in the hippocampus of rat models, in relation to flurazepam (FZP, a member of BDZ) tolerance and dependence, were investigated. Methods: The mRNA of preproNPY and its receptors (Y_1, Y_2, and Y_5) in the hippocampus were determined by competitive RT-PCR, and the distribution of NPY in the hippocampus was examined by immunohistochemistry. Results: A decrease of preproNPY mRNA in the hippocampus was found in tolerant and dependent rats. The level of preproNPY mRNA in the hippocampus was reversely correlated with the degree of tolerance and dependence, measured by the threshold of pentylenetetrazol-induced seizures. Immunohistochemistry indicated a decrease of NPY-immunoreactive material in neurons of the CA1, CA3, and dentate gyrus regions of both tolerant and dependent rats. The mRNA of NPY receptors Y_1 and Y_5 decreased in tolerant rats but did not change in dependent rats. The mRNA of NPY receptor Y_2 increased in tolerant rats but decreased in dependent rats. Conclusion: A decrease of NPY in the hippocampus might be involved in anticonvulsant tolerance and dependence following long-term treatment with FZP. Y_1, Y_2, and Y_5 mRNA were also altered in FZP tolerance and dependence.
机译:目的:抗惊厥耐受性和依赖性是限制苯二氮卓类药物(BDZ)临床使用的两个障碍。为了探讨这两种不良反应的机制,研究了大鼠模型海马中神经肽Y(NPY)及其受体的变化与氟西epa(FZP,BDZ的成员)耐受性和依赖性的关系。方法:采用竞争性RT-PCR技术检测海马中preproNPY及其受体(Y_1,Y_2和Y_5)的mRNA,并通过免疫组织化学方法检测海马中NPY的分布。结果:在耐受和依赖的大鼠中发现海马前proNPY mRNA降低。海马中preproNPY mRNA的水平与耐受性和依赖性程度呈反相关,通过戊四氮诱发癫痫发作的阈值进行测量。免疫组织化学表明,耐性和依赖性大鼠的CA1,CA3和齿状回区域的神经元中NPY免疫反应物质的减少。 NPY受体Y_1和Y_5的mRNA在耐受大鼠中下降,但在依赖大鼠中没有改变。 NPY受体Y_2的mRNA在耐受大鼠中增加,但在依赖大鼠中减少。结论:FZP长期治疗后,海马NPY的降低可能与抗惊厥耐受性和依赖性有关。 Y_1,Y_2和Y_5 mRNA的FZP耐受性和依赖性也发生了改变。

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