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出 处:《中国药理学与毒理学杂志》2014年第4期637-681,共45页Chinese Journal of Pharmacology and Toxicology
摘 要:β连环素及wnt5a在甲基苯丙胺自身给药中的表达变化 摘要:目的初步探讨β连环素,wntl在甲基苯丙胺自身给药后蛋白表达量的变化,从而根据其变化选择相应的特异性拮抗剂或者激动剂以期达到对甲基苯丙胺成瘾的抑制作用。方法采用大鼠静脉自身给药进静脉插管手术的方法来构造大鼠自身给药的模型,再取脑通过免疫印记的方法来检测大鼠脑区蛋白表达量的变化。结果与假手术组相比,甲基苯丙胺给药组的β连环素的表达量在前额皮层,伏隔阂,尾壳核,腹侧被盖区以及海马区均有不同程度的增高;wntl只在腹侧被盖区中的表达量有所升高,而在其他各脑区中的表达量并无差异。结论甲基苯丙胺自身给药会引起wnt信号通路的关键蛋白β连环素表达量的变化,而仅仅影响wntl在腹侧被盖区的表达。Persistent nociception induces anxiety and depres- sion-like behaviors in rats: role of the HCN channel YANG Lu-jia, ZHANG Shu-zhuo, SUN Yah, LIU Xiao-yan, LI Jin, ZHENG Jian-quan Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China Abstract: OBJECTIVE To explore the relationship between hyperpolarization-activated cyclic nucleotidegated channels (HCN) and the comorbid neuropathic pain and mental disorder. METHODS Rat spared nerve injury (SNI) model was setup and ZD7288, an antagonist of HCN channel, was administrated by intracerebroventricular injection. The touch threshold and paw withdrawallatency of SNI rats were measured. The open field, elevated plus maze and forced swimming test were performed. The expression level of HCN channel was tested. RESULTS After SNI surgery, the pain threshold and paw withdrawal latency decreased. The expression level of HCN was increased in hippocampus and thalamus. ZD7288 (5 μg. kg-1 ) could increase the touch threshold significantly and partial ameliorate anxiety as well as depression like behavior. CONCLUSION ZD7288 plays an analgesic effect and ameliorate anxiety as well as depression like behaviors in SNI rats by blocking HCN channels. HCN channel is possibly involve in the comorbid neuropathic pain and mental disorder. Key words: neuropathic pain; HCN channel; ZD7288; anxiety; depression
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