Abstract: Objective To investigate the effects of different concentrations of mirtazapine on anxiety and depression like behavior induced by chronic restraint stress in adolescent mice, so as to provide data for the treatment of adolescent emotional disorders. Methods A total of 60 male C57 mice aged 3 - 4 weeks were randomly selected. The model group was under chronic restraint stress (CRS) 4 hours per day for 10 days. The treatment group was injected with low concentration (15 mg/kg) or high concentration (30 mg/kg) mirtazapine for 10 days. Anxiety like behavior was detected by open-field test (OFT), depression like behavior was detected by tail-suspension test (TST) and force swim test (FST), and serum mirtazapine level was detected by enzyme-linked immunosorbent assay. Results In the OFT experiment, the residence time of CRS mice in the central area was lower than that in the control group[(106.1±36.64)s vs. (182.5±38.69)s, P<0.01). After the application of high concentration mirtazapine (30 mg/kg), the time was extended to (186.1±23.43)s, which was close to the normal level. In the TST experiment, the resting time of CRS group was higher than that of control group[(176.2±104.5)s vs. (71.05±36.4)s, P<0.01]. After the application of high concentration mirtazapine (30 mg/kg), the time was shortened to (69.13±31.72)s (P > 0.05). In FST experiment, the floating time of CRS group was higher than that of control group[(304.6±87.96)s vs. (196.2±72.6)s, P<0.01]. After high concentration mirtazapine (30 mg/kg), the floating time was shortened to (188.8±49.05)s (P> 0.05). CRS resulted in that serum NE [(34.52±9.03)pg/ml] and 5-HT [(44.42±16.55)ng/ml] levels of mice in CRS group were lower than those of normal mice (P<0.01). After application of high concentration mirtazapine, it returned to the normal level (NE:(105.93±21.42)pg/mL,5-HT:(133.56±32.31)ng/mL. Conclusions CRS may lead to depression and anxiety like mood disorder in adolescent mice. Systemic chronic application of high concentration mirtazapine can improve the symptoms of anxiety and depression.

Key words: chronic restraint stress, anxiety, depression, mirtazapine

摘要： 目的 探讨不同浓度米氮平对慢性束缚应激导致的青春期小鼠焦虑、抑郁样行为的改善作用,为青春期情绪障碍的治疗提供研究资料。方法 随机选取60只出生3~4 周龄雄性C57小鼠,模型组给予连续10 d(4 h/d)束缚应激(CRS),治疗组分别连续腹腔注射低浓度(15 mg/kg)或高浓度(30 mg/kg)米氮平(10 d)。分别采用矿场实验(OFT)检测焦虑样行为,悬尾实验(TST)和强迫游泳实验(FST)检测抑郁样行为,酶联免疫法检测血清米氮平水平。结果 OFT实验中,CRS小鼠在中央区停留时间为(106.1±36.64)s,低于对照组[(182.5±38.69)s](P<0.01),应用高浓度米氮平(30 mg/kg)后该时间延长至(186.1±23.43)s,接近正常水平。TST实验中,CRS组静止时间为(176.2±104.5)s,高于对照组[(71.05±36.4)s](P<0.01),应用高浓度米氮平(30 mg/kg)后时间缩短为(69.13±31.72)s(P>0.05)。FST实验中,CRS组的漂浮时间为(304.6±87.96)s,高于对照组[(196.2±72.6)s](P<0.01),应用高浓度米氮平(30 mg/kg)后,漂浮时间缩短为(188.8±49.05)s(P>0.05)。CRS导致小鼠血清NE[(34.52±9.03)pg/ml)]和5-HT[(44.42±16.55)ng/ml]水平低于正常小鼠(P<0.01),应用高浓度米氮平后恢复接近正常水平[NE:(105.93±21.42)pg/ml,5-HT:(133.56±32.31)ng/ml]。结论 CRS可以造成青春期小鼠抑郁和焦虑样情绪障碍,全身慢性应用高浓度米氮平可改善其焦虑和抑郁的症状。

关键词: 慢性束缚应激, 焦虑, 抑郁, 米氮平