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目的建立利血平和对氯苯异丙胺(PCA)诱发小鼠单胺递质耗竭模型,并从自发活动、体温、单胺递质及代谢产物含量等方面探讨两种单胺耗竭模型的异同。方法①利血平诱发小鼠单胺耗竭模型研究:小鼠腹腔注射利血平5 mg·kg-1,18 h后测定自发活动和肛温,断头取脑,高效液相色谱法检测下丘脑组织匀浆5-HT,NE,DA及5-HIAA含量;②PCA诱发小鼠单胺耗竭模型研究:小鼠腹腔注射PCA20 mg·kg-1,6 h后测定自发活动和肛温,断头取脑,高效液相色谱法检测下丘脑组织匀浆5-HT,NE,DA及5-HIAA含量。结果①利血平诱发小鼠单胺耗竭模型研究:与正常对照组相比,利血平组(5 mg·kg-1,ip)小鼠自发活动和肛温显著降低,下丘脑组织匀浆5-HT,NE,DA含量显著降低(分别降低约80%),5-HIAA含量显著升高;②PCA诱发小鼠单胺耗竭模型研究:与正常对照组相比,PCA组(20 mg·kg-1,ip)小鼠自发活动显著增加,肛温显著降低,下丘脑组织匀浆5-HT,NE含量显著降低(分别降低约50%),但PCA对小鼠下丘脑DA及5-HIAA含量无显著影响。结论①利血平和对氯苯异丙胺诱发小鼠单胺耗竭模型建立成功,可用于单胺重摄取抑制剂类抗抑郁剂的靶标和机制研究;②两种模型的相同点:利血平和PCA均可诱发小鼠肛温降低,可并可耗竭5-HT,NE含量;③两种模型的不同点:利血平可同时引起5-HT,NE和DA三种单胺递质耗竭,而PCA仅引起5-HT和NE的含量,且耗竭程度比利血平弱;利血平可引发5-HT代谢产物5-HIAA含量生高,而PCA对5-HIAA含量无影响;利血平对中枢产生抑制作用,而PCA对中枢产生兴奋作用;上述研究表明利血平和PCA引发单胺递质耗竭的作用机制不同。
OBJECTIVE To establish a model of monoamine excretion in mice induced by reserpine and p -chloroacetophenylamine (PCA) and to explore the similarities and differences between the two monoamine depletion models in terms of spontaneous activity, body temperature, monoamine neurotransmitters and metabolites content. Methods ① reserpine-induced monoamine depletion model in mice: mice were injected intraperitoneally reserpine 5 mg · kg-1, 18 h after the determination of spontaneous activity and rectal temperature, decapitated brain, detected by high performance liquid chromatography The content of 5-HT, NE, DA and 5-HIAA in hypothalamus homogenate were measured; ②The model of monoamine depletion in mice induced by PCA: The mice were injected intraperitoneally with PCA 20 mg · kg-1, The content of 5-HT, NE, DA and 5-HIAA in hypothalamus homogenate were determined by brain and HPLC. RESULTS ① Reserpine-induced monoamine depletion model in mice: Compared with the normal control group, spontaneous activities and rectal temperature were significantly decreased in the reserpine group (5 mg · kg -1, ip) mice. Hypothalamus homogenate 5-HT, NE and DA decreased significantly (by about 80%, respectively) and the content of 5-HIAA increased significantly. (2) Compared with the normal control group, PCA group (20 mg · kg -1, ip) mice significantly increased spontaneous activity, rectal temperature was significantly reduced hypothalamic homogenate 5-HT, NE content was significantly reduced (decreased by about 50%, respectively), but the mouse hypothalamus DA and 5-HIAA No significant effect on the content. Conclusions ① The model of monoamine depletion induced by reserpine and p-amphetamine is successfully established and can be used to study the target and mechanism of monoamine reuptake inhibitor-type antidepressants. ② The similarities between the two models: reserpine and PCA Both can reduce the rectal temperature in mice, and may also be depleted of 5-HT, NE content; ③ the difference between the two models: reserpine can also cause 5-HT, NE and DA three monoamine neurotransmitter depletion, and PCA caused only 5-HT and NE levels, and the degree of depletion was weaker than reserpine; reserpine induced 5-HIAA content of 5-HT metabolites, while PCA had no effect on 5-HIAA; On the central inhibitory effect, and PCA on the central excitement effect; these studies show that reserpine and PCA-induced monoamine neurotransmitter depletion mechanism of action is different.