The anxiolytic- and anti-depressant-like effects of ATPM-ET, a novel k agonist and u partial agonist, in mice
The anxiolytic- and anti-depressant-like effects of ATPM-ET, a novel k agonist and u partial agonist, in mice
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ATPM-ET（一种新型 k 激动剂和 u 部分激动剂）在小鼠中的抗焦虑和抗抑郁样作用
DOI：
10.1007/s00213-016-4292-z
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发表时间：
2016
影响因子：
3.4
通讯作者：
Jing-Gen Liu
中科院分区：
文献类型：
--
作者：
Qian Wang;Yu Long;Ai Hang;Gui-Ying Zan;Xiao-Hong Shu;Yu-Jun Wang;Jing-Gen Liu
阿片受体与动机和情绪的调节有关。然而，动物研究表明，κ阿片受体的激活在类焦虑和类抑郁行为模型中产生截然不同的情绪改变作用，因此，κ受体在情绪控制中的作用仍未确定。κ/μ阿片在情绪调节中的作用尚不清楚。目的探讨(-)-3- n -乙基氨基噻唑[5,4-b]- n -环丙基甲基吗啡南盐酸盐（ATPM-ET）作为一种新型κ激动剂和μ部分激动剂对情绪反应的调节作用。方法采用高架迷宫（EPM）、开阔场地试验（OFT）、强迫游泳试验（FST）和悬尾试验（TST）检测ATPM-ET的情绪反应。采用选择性κ拮抗剂no -binaltorphimine （no - bni）和μ拮抗剂β-funaltrexamine （β-FNA）确定受体类型。采用条件场所厌恶模型评价其对厌恶情绪的影响。结果在EPM和OFT中，ATPM-ET（1和2 mg/kg， s.c）分别显著增加了大鼠在张开臂和中央区域停留的时间。在FST和TST中，ATPM-ET（0.5和1 mg/kg， s.c）显著缩短了静止时间。非bni （10 mg/kg, i.p,−24 h）可以阻止这些影响，但β-FNA（10和20 mg/kg， i.p,−24 h）预处理不能阻止这些影响。在2 mg/kg剂量下，ATPM-ET不诱导条节性地方厌恶。结论satpm - et在0.5 ~ 2mg /kg剂量范围内具有抗焦虑和抗抑郁样作用，且不引起反感情绪。κ受体的激活比μ受体的激活更密切地介导了这些作用。
RationaleOpioid receptors are implicated in the regulation of motivation and emotion. However, animal studies show that activation of κ opioid receptor produces contrasting mood-altering effects in models of anxiety-like and depressive-like behaviors, and consequently, the role of κ receptor in mood control remains unsettled. The effect of κ/μ opioid combination in emotion regulation was unexplored.ObjectivesThe aim of the study was to investigate the effects of (-)-3-N-ethylaminothiazolo [5,4-b]-N-cyclopropylmethylmorphinan hydrochloride (ATPM-ET), a novel κ agonist and μ partial agonist, in regulating emotional responses.MethodsThe emotional responses of ATPM-ET were detected in the elevated plus maze (EPM), open field test (OFT), forced swim test (FST), and tail suspension test (TST). Selective κ antagonist nor-binaltorphimine (nor-BNI) and μ antagonist β-funaltrexamine (β-FNA) were applied to determine the type of receptor involved. The conditioned place aversion model was used to evaluate the effects on aversive emotion.ResultsIn the EPM and OFT, ATPM-ET (1 and 2 mg/kg, s.c.) significantly increased the time spent in the open arm and in the central area, respectively. In the FST and TST, ATPM-ET (0.5 and 1 mg/kg, s.c.) significantly reduced the duration of immobility. These effects were prevented by nor-BNI (10 mg/kg, i.p., −24 h), but not by β-FNA (10 and20 mg/kg, i.p., −24 h) pretreatment. At the dose of 2 mg/kg, ATPM-ET did not induce conditioned place aversion.ConclusionsATPM-ET, at doses from 0.5 to 2 mg/kg, produced anxiolytic- and antidepressant-like effects without inducing aversive emotion. These effects were more closely mediated by activation of κ receptor than μ receptor.