Nejati Shahrzad, Khakpai Fatemeh, Zarrindast Mohammad-Reza
Department of Pharmacology and Toxicology, Islamic Azad University, Pharmaceutical Science Branch (IAUPS), Tehran, Iran.
Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Brain Res. 2020 May 1;1734:146701. doi: 10.1016/j.brainres.2020.146701. Epub 2020 Feb 15.
In the present study, the effects of intraperitoneal (i.p.) injections of citalopram and citicoline on morphine-induced anxiolytic effects were investigated in non-sensitized and morphine-sensitized mice using elevated plus-maze (EPM). Subcutaneous (s.c.) administration morphine (5 mg/kg) increased the percentage of open arm time (%OAT, in morphine-sensitized mice), and open arm entries (%OAE, in non-sensitized mice), but not a locomotor activity, indicating an anxiolytic response to morphine. On the other hand, i.p. administration of naloxone decreased %OAT (morphine-sensitized mice), and %OAE (non-sensitized and morphine-sensitized mice), but not a locomotor activity, showing an anxiogenic effect to naloxone. Moreover, i.p.co-administration of citalopram (5 and 10 mg/kg) and citicoline (75 mg/kg) induced the anxiolytic effect. Interestingly, i.p. co-administration of low doses of citalopram (0.5, 1 and 2.5 mg/kg) and citicoline (25 mg/kg) significantly increased %OAT and %OAE in non-sensitized as well as %OAT in morphine-sensitized mice, indicating an anxiolytic effect. An isobolographic analysis of data was performed, presenting a synergistic interaction between citalopram and citicoline upon the production of anxiolytic effect in non-sensitized and morphine-sensitized mice. In conclusion, it seems that (1) morphine sensitization affects the anxiety behavior in the EPM, (2) μ-opioid receptors play an important role in morphine anxiolytic effect, (3) citalopram and citicoline induced anti-anxiety effect, (4) a synergistic effect of citalopram and citicoline upon induction of anti-anxiety behavior in non-sensitized and morphine-sensitized mice.
在本研究中，使用高架十字迷宫（EPM），在未致敏和吗啡致敏的小鼠中研究了腹腔注射西酞普兰和胞磷胆碱对吗啡诱导的抗焦虑作用的影响。皮下注射吗啡（5毫克/千克）增加了开放臂时间百分比（%OAT，在吗啡致敏小鼠中）和开放臂进入次数（%OAE，在未致敏小鼠中），但不影响运动活性，表明对吗啡有抗焦虑反应。另一方面，腹腔注射纳洛酮降低了%OAT（吗啡致敏小鼠）和%OAE（未致敏和吗啡致敏小鼠），但不影响运动活性，显示出纳洛酮有致焦虑作用。此外，腹腔联合注射西酞普兰（5和10毫克/千克）和胞磷胆碱（75毫克/千克）诱导了抗焦虑作用。有趣的是，腹腔联合注射低剂量的西酞普兰（0.5、1和2.5毫克/千克）和胞磷胆碱（25毫克/千克）显著增加了未致敏小鼠的%OAT和%OAE以及吗啡致敏小鼠的%OAT，表明有抗焦虑作用。对数据进行了等效应线分析，结果显示西酞普兰和胞磷胆碱在未致敏和吗啡致敏小鼠产生抗焦虑作用时存在协同相互作用。总之，似乎（1）吗啡致敏影响EPM中的焦虑行为，（2）μ-阿片受体在吗啡抗焦虑作用中起重要作用，（3）西酞普兰和胞磷胆碱诱导抗焦虑作用，（4）西酞普兰和胞磷胆碱在未致敏和吗啡致敏小鼠诱导抗焦虑行为时具有协同作用。
