5-HT2C receptor activation prevents stress-induced enhancement of brain 5-HT turnover and extracellular levels in the mouse brain: modulation by chronic paroxetine treatment
5-HT2C receptor activation prevents stress-induced enhancement of brain 5-HT turnover and extracellular levels in the mouse brain: modulation by chronic paroxetine treatment
复制标题
DOI：
10.1111/j.1471-4159.2010.06932.x
复制
发表时间：
2010-10-01
影响因子：
4.7
通讯作者：
Lanfumey, Laurence
中科院分区：
文献类型：
--
作者：
Mongeau, Raymond;Martin, Cedric B. P.;Lanfumey, Laurence
已知压力会激活中枢5-羟色胺（5-HT）系统，这可能是涉及几种5-HT受体的应对反应的一部分。虽然5-HT 2C受体是众所周知的，涉及焦虑，他们参与的压力引起的变化还没有在行为和神经化学水平平行调查。我们在这里表明，优先5-HT 2C受体激动剂，间氯苯哌嗪，以及约束压力增加焦虑的小鼠社会互动测试。选择性5-HT 2C受体拮抗剂SB 242，084可预防这两种致焦虑作用。束缚应激增加了不同脑区的5-HT周转，5-HT 2B/2C受体激动剂RO 60-0175（1 mg/kg）可阻止这种作用，但优先使用的5-HT 2A激动剂1-（2，5-二甲氧基-4-碘苯基）-2-氨基丙烷（1 mg/kg），与之相反，SB 242，084（1 mg/kg）增强，这也阻断了RO 60-0175的作用。使用微透析，RO 60-0175显示出抑制皮质5-HT溢出在应激小鼠时，5-HT再摄取被局部阻断。长期帕罗西汀阻止了间氯苯哌嗪的焦虑作用和RO 60-0175对运动和应激诱导的5-HT周转增加的抑制作用。慢性帕罗西汀的抗焦虑作用可能与5-HT 2C受体介导的抑制应激诱导的5-HT释放增加引起的5-HT神经传递增强有关。
Stress is known to activate the central 5-hydroxytryptamine (5-HT) system, and this is probably part of a coping response involving several 5-HT receptors. Although 5-HT2C receptors are well known to be implicated in anxiety, their participation in stress-induced changes had not been investigated in parallel at both behavioral and neurochemical levels. We show here that the preferential 5-HT2C receptor agonist, m-chlorophenylpiperazine, as well as restraint stress increased anxiety in the mouse social interaction test. The selective 5-HT2C receptor antagonist, SB 242,084, prevented both of these anxiogenic effects. Restraint stress increased 5-HT turnover in various brain areas, and this effect was prevented by the 5-HT2B/2C receptor agonist RO 60-0175 (1 mg/kg), but not the preferential 5-HT2A agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1 mg/kg), and in contrast potentiated by SB 242,084 (1 mg/kg), which also blocked the effect of RO 60-0175. Using microdialysis, RO 60-0175 was shown to inhibit cortical 5-HT overflow in stressed mice when 5-HT reuptake was blocked locally. Chronic paroxetine prevented both the anxiogenic effect of m-chlorophenylpiperazine and the inhibitory effect of RO 60-0175 on locomotion and stress-induced increase in 5-HT turnover. The anxiolytic action of chronic paroxetine might be associated with an enhancement of 5-HT neurotransmission caused by a decreased 5-HT2C receptor-mediated inhibition of stress-induced increase in 5-HT release.