育亨宾对应激大鼠蓝斑核去甲肾上腺素释放的影响

Effects of yohimbine on norepinephrine release by locus coeruleus in stressed rats

目的 在体电刺激蓝斑核,探讨抑郁样行为模型大鼠下丘脑内的去甲肾上腺素（NE）释放调控机制.方法 应用慢性不可预见性应激刺激结合孤养建立抑郁样行为大鼠模型,通过行为学检测观察造模是否成功.在体电刺激两组大鼠蓝斑核,应用碳纤维电极测量技术记录下丘脑内NE的释放量,分析两组大鼠NE释放信号的峰值、达峰时间和半衰期三个指标.结果 行为学检测表明模型组大鼠的体质量[（263.9±16.4）g]、旷场实验得分[（19.4±7.9）分]和糖水偏爱百分比[（44.3±10.8）％]低于对照组[（314.3±24.3）g,（53.3±19.0）分,（60.6±13.3）％]（P＜0.01）.电刺激蓝斑核,在下丘脑通过微碳纤电极检测NE释放,模型组大鼠NE释放的峰值[（176.9±50.4） pA]比对照组大鼠减少[（361.6±88.6） pA] （P＜0.01）,达峰时间缩短（P＜0.05）;在腹腔注射α2受体拮抗剂育亨宾（3 mg/kg）后,模型组大鼠NE释放的峰值和达峰时间均明显增大,差异有统计学意义.对照组大鼠用育亨宾（3 mg/kg）后NE信号的峰值和达峰时间虽然有所增加,但差异无统计学意义.结论 慢性不可预见性应激导致的抑郁样行为模型大鼠的蓝斑核投射到下丘脑的神经末梢释放的NE减少;育亨宾可以通过抑制突触前α2受体增加模型组大鼠蓝斑核投射至下丘脑NE的释放.结果提示蓝斑投射到下丘脑的去甲肾上腺素能通路可能参与到抑郁症的发生.

Objective To study the cellular and molecular modulation mechanisms of norepinephrine （NE） release in hypothalamus induced by electrical stimulation in locus coeruleus （LC） in the rat model of depression-like behavior.Methods The depression-like behavior model was established by combining separation and chronic unpredictable stress stimulations.After the model establishment,behavior tests were used to verify the success of modeling.NE release in the hypothalamus induced by electrical stimulation in LC was studied in real time and NE signal was recorded with carbon fiber electrode.The peak value,the time to peak and half-life period of NE signal in both group rats were measured and analysed.Results The bodyweight,score of open-field test,percentage of sucrose preference of model group rats （（263.9± 16.4） g,（19.4±7.9）,（44.3± 10.8） %） were significantly lower than those（（314.3±24.3） g,（53.3± 19.0）,（60.6± 13.3） %） of control group（P〈0.01）.The peak value of NE signal in the hypothalamus induced by electrical stimulation in locus coeruleus in depression-like behavior model rats（（176.9±50.4） pA）was less than that（（361.6±88.6） pA）in control group（P〈0.01）,and the time to peak of NE signal was also shortened in depression-like behavior model group rats （P〈0.05）.Intraperitoneal injection of yohimbine （3 mg/kg） potentiated electrical stimulation induced NE release in depression-like behavior model rats but not in control group.Conclusion The chronic unpredictable stresses attenuate the secretion of NE in the hypothalamus induced by electrical stimulation in LC in rats.Yohimbine,a presynaptic α2 receptor antagonist,increased NE release in hypothalamus in depression-like behavior model rats.These findings suggest that the LC projects functionally to the hypothalamus and the projection may contribute to the pathogenesis of depression.