The anxiety caused by morphine protracted abstinence is considered to be an important factor contributes to drug-seeking and relapse. Endoplasmic reticulum (ER) stress plays important roles in many kinds of mental disorders including drug addiction and anxiety, but it is unclear whether ER stress is involved in anxiety-like behaviors induced by morphine withdrawal. In this study, by using behavioral test, western blot, immunofluorescence, electron transmission microscope, we found that: (1) Inhibition of endoplasmic reticulum stress by 4-Phenylbutyric acid (4-PBA) could attenuate anxiety-like behaviors induced by morphine withdrawal. (2) The endoplasmic reticulum stress-related proteins in the lateral habenula (LHb) but not in the nucleus accumbens (NAc), ventral pallidum (VP), basolateral amygdala (BLA) and CA1 of hippocampus was upregulated by morphine withdrawal, upregulation of endoplasmic reticulum stress-related proteins in the lateral habenula induced by morphine withdrawal was inhibited by 4-PBA. (3) Endoplasmic reticulum stress-related protein CHOP and eIF2α were expressed in neurons but not in microglia in the LHb. (4) Morphine withdrawal induced neuronal morphological change in the LHb, which was attenuated by 4-PBA.

中文翻译：

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抑制内质网应激可减轻吗啡长期戒断引起的雄性小鼠焦虑样行为

吗啡长期戒断引起的焦虑被认为是导致吸毒和复吸的重要因素。内质网（ER）应激在包括药物成瘾和焦虑在内的多种精神障碍中发挥重要作用，但目前尚不清楚内质网应激是否与吗啡戒断引起的焦虑样行为有关。本研究通过行为学测试、蛋白质印迹、免疫荧光、电镜观察发现：（1）4-苯基丁酸（4-PBA）抑制内质网应激可减轻吗啡戒断引起的焦虑样行为。 (2)吗啡戒断后，外侧缰核(LHb)内质网应激相关蛋白上调，而伏隔核(NAc)、腹侧苍白球(VP)、基底外侧杏仁核(BLA)和海马CA1中无内质网应激相关蛋白上调， 4-PBA 抑制吗啡戒断诱导的外侧缰核内质网应激相关蛋白。 (3)内质网应激相关蛋白CHOP和eIF2α在LHb的神经元中表达，但在小胶质细胞中不表达。 (4)吗啡戒断引起LHb神经元形态变化，4-PBA减弱这种变化。