西酞普兰与蝇蕈醇对雄性小鼠抗焦虑和抗抑郁样作用诱导的协同效应：等效线分析
Synergistic effect between citalopram and muscimol upon induction of anxiolytic- and antidepressant-like effects in male mice: An isobologram analysis.
作者信息
Amini Elnaz, Shokrnejad-Namin Taha, Zarrindast Mohammad-Reza, Khakpai Fatemeh
机构信息
Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
出版信息
IBRO Neurosci Rep. 2024 Feb 10;16:353-360. doi: 10.1016/j.ibneur.2024.02.003. eCollection 2024 Jun.
BACKGROUND
There is evidence that both the GABAergic system and serotonin reuptake inhibitor (SSRI) such as citalopram are involved in the modulation of anxiety and depression processes. In this research, we examined the effects of GABA receptor agents and citalopram on anxiety- and depression-related behaviors and their interaction in male mice.
METHODS
For intracerebroventricular (i.c.v.) infusion, a guide cannula was implanted in the left lateral ventricle. Anxiety and depression behaviors were evaluated using the elevated plus-maze (EPM) and forced swimming test (FST).
RESULTS
The results revealed that i.c.v. microinjection of muscimol (1 µg/mouse) enhanced % OAT (open arm time) and % OAE (open arm entries) in the EPM test and decreased immobility time in the FST without affecting locomotor activity, presenting anxiolytic- and antidepressant-like behaviors in the EPM and FST, respectively. On the other hand, i.c.v. microinjection of bicuculline (1 µg/mouse) reduced % OAT and % OAE without affecting locomotor activity and immobility time, presenting an anxiogenic-like effect. Moreover, i.p. administration of citalopram (8 mg/kg) increased %OAT and %OAE and reduced immobility time with no effect on locomotor activity, showing anxiolytic- and antidepressant-like responses in male mice. Furthermore, i.c.v. infusion of an ineffective dosage of muscimol potentiated the anxiolytic- and antidepressant-like responses induced by i.p. injection of citalopram in male mice. When citalopram and bicuculline were co-injected, a non-significant dose of bicuculline reversed the anxiolytic-like effect of citalopram in male mice. Also, the data revealed synergistic anxiolytic- and antidepressant-like behaviors between citalopram and muscimol in male mice.
CONCLUSIONS
The results suggested an interaction between citalopram and GABAergic agents on the modulation of anxiety and depression behaviors in male mice.
背景
有证据表明，γ-氨基丁酸（GABA）能系统和5-羟色胺再摄取抑制剂（SSRI）如西酞普兰均参与焦虑和抑郁过程的调节。在本研究中，我们检测了GABA受体激动剂和西酞普兰对雄性小鼠焦虑和抑郁相关行为的影响及其相互作用。
方法
为进行脑室内（i.c.v.）注射，在左侧脑室植入引导套管。使用高架十字迷宫（EPM）和强迫游泳试验（FST）评估焦虑和抑郁行为。
结果
结果显示，脑室内微量注射蝇蕈醇（1微克/小鼠）可增加EPM试验中的开臂时间百分比（%OAT）和开臂进入次数百分比（%OAE），并减少FST中的不动时间，且不影响运动活性，分别在EPM和FST中呈现出抗焦虑和抗抑郁样行为。另一方面，脑室内微量注射荷包牡丹碱（1微克/小鼠）可降低%OAT和%OAE，且不影响运动活性和不动时间，呈现出致焦虑样效应。此外，腹腔注射西酞普兰（8毫克/千克）可增加%OAT和%OAE，并减少不动时间，对运动活性无影响，在雄性小鼠中表现出抗焦虑和抗抑郁样反应。此外，脑室内注射无效剂量的蝇蕈醇可增强腹腔注射西酞普兰对雄性小鼠诱导的抗焦虑和抗抑郁样反应。当西酞普兰和荷包牡丹碱共同注射时，非显著剂量的荷包牡丹碱可逆转西酞普兰对雄性小鼠的抗焦虑样效应。此外，数据显示西酞普兰和蝇蕈醇在雄性小鼠中具有协同抗焦虑和抗抑郁样行为。
结论
结果表明，西酞普兰和GABA能药物在雄性小鼠焦虑和抑郁行为的调节上存在相互作用。
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