激活中枢5-HT_(2A)受体抑制慢性不可预见性应激模型大鼠中缝背核5-羟色胺的分泌

Central serotonin type 2A receptor activation inhibits serotonin release from dorsal raphe nucleus in chronic unpredictable stress induced depression rats

目的:5-HT2A受体在应激反应中调节5-羟色胺(5-HT)系统的功能。本研究试图揭示大鼠5-HT2A受体在中缝背核到前边缘皮质通路释放5-HT的调节作用。方法:用慢性不可预见性刺激建立抑郁样行为大鼠模型,根据旷场实验评分和糖水偏爱百分比等行为学指标判断大鼠是否造模成功。电刺激麻醉大鼠的中缝背核,用碳纤维电极恒流安培法检测大鼠前边缘皮质部位5-HT的释放。结果:大鼠腹腔注射5-HT2A受体拮抗剂ketanserin(i.p.2 mg/kg)增强前边缘皮质5-HT的释放(P<0.05)。另外,脑室注射5-HT2A/2C受体激动剂DOI(i.c.v.20μg)减少5-HT的释放(P<0.01)。结论:电刺激大鼠中缝背核,在前边缘皮质检测到的5-HT的释放受中枢5-HT2A受体的调节,激活5-HT2A受体抑制前边缘皮质部位5-HT的释放。

AIM- 5-HT：A receptors play a par- ticularly important role in mediating serotonin＇s ac- tion during stress. The precise action of this receptor on serotonin release remains unclear. The present study is to explore how 5-HT2A receptors mediated serotonin release via dorsal raphe nucleus projecting to the prelimbic cortex. METHODS： Male Spra- gue-Dawley rats （180-200 g） were randomly separa- ted into control group and model group. Model group rats were established with a series of chronic unpre- dictable stress （CUS）. Behavioral indexes in open field test and sucrose preference test were measured to confirm the presence of depression. Furthermore, constant amperometric method with carbon fiber e- lectrode was used to detect neurotransmitter release in prelimbic cortex induced by electrical stimulation of the dorsal raphe nucleus in anesthetized rats. RESULTS：The systemic administration of 5-HT2A re- ceptor antagonist, ketanserin （ i.p. 2 mg/kg ）, augmented the local release of 5-HT in prelimbic cortex （P 〈 0.05）. On the other hands, central ap- plication of the 5-HT2A/2C agonist DOI （ i. c. v. 20 p,g ） decreased the local release of 5-HT （P 〈 0.01 ）. CONCLUSION： These findings suggest that the extracellular 5-HT level in the prelimbic cortex induced by electrical-stimulation of the dorsal raphe nucleus was inhibited by 5-HT2A receptors activation, and was enhanced by 5-HT2A receptors an- tagonist.