胍丁胺在药物诱发抑郁模型上的药效评价

Evaluation of the Antidepressant Effect of Agmatine in Pharmacological Depression Models

目的在药物诱发抑郁模型上观察胍丁胺(Agmatine,AG)的抗抑郁作用及可能的作用机制。方法采用小鼠5羟色胺酸(5hydroxytryptophan,5HTP)增强实验,小鼠育亨宾(yohimbine,YOH)毒性增强实验,小鼠阿朴吗啡(apomorphine,APO)诱导体温下降和利血平(reserpine,RES)诱导体温下降实验探讨AG抗抑郁作用及可能的作用环节。用VIDEOMEXV型图像运动解析仪检测小鼠自发活动行为。结果在小鼠5HTP增强实验模型上,单次ig给予AG10～20mg·kg-1剂量,或多次ig给予AG10～80mg·kg-1(qd,连续3d),对5HTP诱导的小鼠甩头行为均具有显著增强作用。在小鼠YOH毒性增强实验模型上,多次ig给予AG10～160mg·kg-1(qd,连续3d),均未见增强YOH毒性作用。在小鼠APO诱导体温下降实验模型上,ig给予AG10～80mg·kg-1(qd,连续7d),对APO16mg·kg-1诱导的降温和AUC0～30均未见显著性的拮抗作用。在小鼠RES诱导体温下降实验模型上,ig给予AG10～80mg·kg-1(qd,连续7d),对RES1mg·kg-1诱导的降温和AUC0～6均有显著的拮抗作用。小鼠ig给予AG10～80mg·kg-1(qd,连续3d)对自发活动无显著性改变。结论AG在药理学抑郁模型有显著的抗抑郁活性。并且其抗抑郁活性与增强5羟色胺(5HT)神经系统功能有关,而与去甲肾上腺素能(NE)神经功能无关。AG在抗抑郁有效剂量范围内无中枢兴奋或抑制性作用。

Aim To explore the antidepressant effects and the possible mechanism of agmatine（AG）in pharmacological depression models. Methods The 5-hydroxytryptophan potentiation test, yohimbine toxicity potentiation test, apomorphineinduced hypothennia test and reseponie-induced hypothennia test in mice were used in this study. Results Repeated administration with AG（ 10,20,40,80mg·kg^-1 ig for 1 time per day for 7d）significantly antagonized the reserpine（ 1mg·kg^-1, iv）induced hypothennia or the AUC0- 6 of the time-temperature curve in mice. AG in a single dose 10, 20mg·kg^-1 （ig） or multiple doses （ 10,20,40,80mg·kg^-1, ig for 1 time per day for 3d） significantly increased the symptom of head-twitches in the 5-hydroxytryptophan （5-HTP） potentiation test the mice. Agmatine （ 10 - 160mg·kg^-1, ig 1 time per day for 3d）didn＇t increase the yohimbine toxicity in mice. Repeated administration with AG （10,20,40,80mg·kg^-1,ig for 1 time per day for 7d）had no significant effect on the apomorphine（ 16mg·kg^-1 ip）induced hypothermia or this AUC0-30 in mice. Also,AG（10,20,40,80mg·kg^-1 ,ig for 1 time per day for 3d） had no significant effect on the spontaneous motor activity in mice. Conclusion AG has antidepressant effect in pharmacological depression models, which is closely related to the potentiation of central 5-HT system rather than to the central NE system.