不同抗抑郁药在小鼠体内的时辰药理学研究

Chronopharmacological study of different antidepressants in mice

目的初步探索不同给药时间对7种抗抑郁药在小鼠体内抗抑郁效果的影响。方法雄性小鼠随机分为8组,每组各36只:文拉法辛组(75 mg/kg)、舍曲林组(20 mg/kg)、氟西汀组(20 mg/kg)、多塞平组(15 mg/kg)、米氮平组(15 mg/kg)、西酞普兰(40 mg/kg)、曲唑酮组(50 mg/kg)和对照组(生理盐水)。分别在明相(9:00、13:00、17:00)和暗相(21:00、1:00、5:00)6个时间点前30 min采用相应药物灌胃给药,每个时间点灌胃6只小鼠,给药体积为0.1 m L/10 g,30min后采用强迫游泳实验测定这7种抗抑郁药抗抑郁作用效果。结果在各时间点上,与对照组相比,文拉法辛组和舍曲林组小鼠的不动时间均缩短(均P<0.05)。文拉法辛、氟西汀、米氮平、多塞平组在暗相的不动时间短于明相(均P<0.05);而舍曲林组小鼠在暗相晚期(5:00)和明相早期(9:00)的不动时间较其他时间点缩短(P<0.05)。结论大多数抗抑郁药抗抑郁作用效果存在24 h节律,但不同抗抑郁药其节律模式并非完全一致,有待进一步开展这些抗抑郁药时辰药理学的作用机制及临床研究。

Objective To explore the influence of different administration time on antidepressant effect of seven clinical common antidepressants. Methods Male mice were randomly divided into eight groups：venlafaxine （75 mg/kg）, sertraline （20 mg/kg）, fluoxetine （20 mg/kg）, doxepin （15 mg/kg）, mirtazapine （15 mg/kg）, citalopram （40 mg/kg）, trazodone （50 mg/kg） and control （saline） groups. Each group contained 36 mice. Drugs were administered to 6 mice per group 30 min before forced swimming test at the 6 time points （9：00, 13：00 and 17：00 as light phase and 21：00, 1：00 and 5：00 as dark phase）. Forced swimming test was applied to determine the influence of dosing time on anti-immobility effect of seven antidepressants at each time point. Results Immobility time in venlafaxine group and sertraline group significant？ly decreased compared with that of control group at all time points（all P〈0.05）. Moreover, anti-immobility effects of ven？lafaxine, fluoxetine, mirtazapine and doxepin were better during the dark phase than during the light phase （all P〈0.05）. In addition, immobility time in sertraline group decreased at the late part of dark phase （5：00） and the early part of light phase （9：00） compared with other phases （P〈0.05）. Conclusions Most antidepressants show 24-h rhythm dependent an？ti-immobility effects, but rhythmic patterns are not completely consistent among different antidepressants. Further study is needed to explore the chronopharmacological mechanism and clinical applications of these antidepressants.