氟西汀和阿米替林对大鼠强迫游泳试验的行为表现及脑内信号分子ERK1／2磷酸化水平的影响

Effects of fluoxetine and amitriptyline on rat behaviors in forced swimming test and phosphorylated ERK1/2 level in rat brain

目的观察氟西汀和阿米替林对大鼠强迫游泳试验中各种行为表现及脑内信号分子细胞外调节蛋白激酶（ERK1／2）磷酸化水平的影响。方法30只雄性SD大鼠先预游15min，间隔23h后，按随机数字表法分成3组：氟西汀组、阿米替林组和对照组，每组各10只。氟西汀、阿米替林按20mg／kg腹腔注射给药．对照组腹腔注射等体积的蒸馏水，1h后进行5min的游泳测试，录像并记录出现不动行为的潜伏期和不动、游泳及攀抓行为的时间。游泳完毕后将大鼠灌流处死，对脑组织进行磷酸化ERK1／2（pERK1／2）免疫组织化学染色，观察pERK1／2阳性神经元在部分脑区的分布。结果（1）阿米替林组不动行为潜伏期明显长于对照组，攀抓行为时间明显长于对照组和氟西汀组．不动行为时间明显少于对照组；氟西汀组游泳行为时间明显长于对照组和阿米替林组；以上差异均有统计学意义（P〈0．05）。（2）氟西汀组前额皮质、扣带回及边缘前皮质脑区中pERK1／2阳性神经元数目较对照组和阿米替林组明显减少；阿米替林组腹外侧隔核中pERK1／2阳性神经元数目较对照组明显减少：两给药组下丘脑室旁核中pERK1／2阳性神经元数目较对照组均明显减少，其中阿米替林组减少幅度更大；以上差异均有统计学意义（P〈0．05）。结论阿米替林和氟西汀能对大鼠强迫游泳试验的行为表现产生不同影响，二者可能都有降低负性心理应激反应的作用，脑内ERK1／2信号通路可能参与其中。

Objective To investigate the effects of fluoxetine and amitriptyline on rat behaviors in the forced swimming test （FST） and phosphorylated ERK1/2 level in the rat brain. Methods Thirty male SD rats were randomly divided into three groups （n=10）： fluoxetine （FLX）, amitriptyline （AMT） and control （CON） groups. Treated groups were injected with 20 mg/kg fluoxetine and 20 mg/kg amitriptyline, respectively, 23 h after the 15-min pre-test of FST. The animals in CON group were injected with the same volume of distilled water. Then a 5-min FST was conducted l h later. The 5-min test sessions were videotaped and the time span for each behavior （latency of immobility, immobility, swimming and climbing） was recorded. All rats were sacrificed with a perfusion of 4% paraformaldehyde immediately after the termination of the test. Immunohistochemical ABC staining was used to observe the distribution of pERK1/2-1ike immunoreactive （LI） neurons in the brain. Results （1） The latency of immobility in AMT group was significantly longer than that of CON group during the 5 min FST （P〈 0.05）, and the climbing time in AMT group was longer than that of CON group and FLX group （P〈0.05）, while the duration of immobility in AMT group was obviously shorter in comparison with CON group （P〈0.05）. The duration of swimming behavior in FLX group was longer than that of CON group as well as AMT group （P〈0.05）. （2） Numbers ofpERK1/2-LI neurons in FLX group were greatly reduced in prefrontal cortex （PFC）, cingulate gyrus （Cg） and prelimbic cortex （Prl） in comparison with that of CONand AMT group （P〈0.05）, while the expressed pERK1/2 in AMT group was significantly decreased in the neurons of ventrolateral septum （LSV） in comparison with that of CON group （P〈0.05）. And compared with CON group, the numbers ofpERK1/2-LI neurons in both drug treated groups were greatly reduced in hypothalamic paraventricular nucleus （PVN） and more significantly in AMT group （P〈0.01）. Conclusion Administration of fluoxetine and amitriptyline have different effects on rat behaviorals in the FST. Both of them may be have some effects on anti-negative psychological stress. The ERK1/2 pathway possibly plays a role in this process.