摄取抑制和自身受体激活在大鼠额叶皮质和背侧海马5-羟色胺释放控制中的作用。
Role of uptake inhibition and autoreceptor activation in the control of 5-HT release in the frontal cortex and dorsal hippocampus of the rat.
作者信息
Hervás I, Queiroz C M, Adell A, Artigas F
机构信息
Department of Neurochemistry, Institut d'Investigacions Biomèdiques de Barcelona, Spain.
出版信息
Br J Pharmacol. 2000 May;130(1):160-6. doi: 10.1038/sj.bjp.0703297.
Abstract
- Using brain microdialysis, we compared the relative role of 5-hydroxytryptamine (5-HT; serotonin) blockade and somatodendritic 5-HT(1A) and/or terminal 5-HT(1B) autoreceptor activation in the control of 5-HT output. 2. Fluoxetine (10 mg kg(-1) i.p.) doubled the 5-HT output in frontal cortex and dorsal hippocampus. The 5-HT(1A) receptor antagonist WAY 100635, (0.3 mg kg(-1) s.c.) potentiated the effect of fluoxetine only in frontal cortex (to approximately 500 % of baseline). 3. Methiothepin (10 mg kg(-1) s.c.) further enhanced the 5-HT rise induced by fluoxetine+WAY 100635, to 835+/-179% in frontal cortex and 456+/-24% in dorsal hippocampus. Locally applied, methiothepin potentiated the fluoxetine-induced 5-HT rise more in the former area. 4. The selective 5-HT(1B) receptor antagonist SB-224289 (4 mg kg(-1) i.p.) enhanced the effect of fluoxetine (10 mg kg(-1) i.p.) in both areas. As with methiothepin, SB-224289 (4 mg kg(-1) i.p.) further enhanced the 5-HT increase produced by fluoxetine+WAY 100635 more in frontal cortex (613+/-134%) than in dorsal hippocampus (353+/-59%). 5. Locally applied, fluoxetine (10 - 300 microM; EC(50)=28 - 29 microM) and citalopram (1 - 30 microM; EC(50)=1.0 - 1.4 microM) increased the 5-HT output two to three times more in frontal cortex than in dorsal hippocampus. These data suggest that the comparable 5-HT increase produced by systemic fluoxetine in frontal cortex and dorsal hippocampus results from a greater effect of reuptake blockade in frontal cortex that is offset by a greater autoreceptor-mediated inhibition of 5-HT release. As a result, 5-HT autoreceptor antagonists preferentially potentiate the effect of fluoxetine in frontal cortex.
摘要
- 我们采用脑微透析技术，比较了5-羟色胺（5-HT；血清素）阻断以及树突-胞体5-HT(1A)和/或终末5-HT(1B)自身受体激活在调控5-HT释放中的相对作用。2. 氟西汀（10毫克/千克，腹腔注射）使额叶皮质和背侧海马体中的5-HT释放量增加了一倍。5-HT(1A)受体拮抗剂WAY 100635（0.3毫克/千克，皮下注射）仅在额叶皮质增强了氟西汀的作用（增至基线的约500%）。3. 甲硫噻嗪（10毫克/千克，皮下注射）进一步增强了氟西汀+WAY 100635诱导的5-HT升高，在额叶皮质升至835±179%，在背侧海马体升至456±24%。局部应用时，甲硫噻嗪在额叶皮质对氟西汀诱导的5-HT升高的增强作用更大。4. 选择性5-HT(1B)受体拮抗剂SB-224289（4毫克/千克，腹腔注射）在两个区域均增强了氟西汀（10毫克/千克，腹腔注射）的作用。与甲硫噻嗪一样，SB-224289（4毫克/千克，腹腔注射）在额叶皮质（613±134%）比在背侧海马体（353±59%）更能进一步增强氟西汀+WAY 100635所产生的5-HT增加。5. 局部应用时，氟西汀（10 - 300微摩尔；半数有效浓度[EC(50)]=28 - 29微摩尔）和西酞普兰（1 - 30微摩尔；EC(50)=1.0 - 1.4微摩尔）在额叶皮质使5-HT释放量增加的幅度比在背侧海马体大两到三倍。这些数据表明，全身应用氟西汀在额叶皮质和背侧海马体产生的相当的5-HT增加，是由于额叶皮质中再摄取阻断作用更强，但被5-HT释放的自身受体介导的更强抑制所抵消。因此，5-HT自身受体拮抗剂优先增强氟西汀在额叶皮质的作用。
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本文引用的文献
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A microdialysis study of the in vivo release of 5-HT in the median raphe nucleus of the rat.一项关于大鼠中缝核体内5-羟色胺释放的微透析研究。
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Effect of fluoxetine on extracellular 5-hydroxytryptamine in rat brain. Role of 5-HT autoreceptors.氟西汀对大鼠脑内细胞外5-羟色胺的影响。5-羟色胺自身受体的作用。
Eur J Pharmacol. 1998 Sep 25;358(1):9-18. doi: 10.1016/s0014-2999(98)00579-2.
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In vivo control of 5-hydroxytryptamine release by terminal autoreceptors in rat brain areas differentially innervated by the dorsal and median raphe nuclei.大鼠脑区中5-羟色胺释放受终末自身受体的体内调控，这些脑区由背侧和中缝核进行不同程度的神经支配。
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Differential effects of 5-HT1B/1D receptor antagonists in dorsal and median raphe innervated brain regions.5-HT1B/1D受体拮抗剂在中缝背核和中缝正中核支配的脑区中的差异效应。
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The selective 5-HT1B receptor inverse agonist 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2, 4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro- spiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289) potently blocks terminal 5-HT autoreceptor function both in vitro and in vivo.选择性5-HT1B受体反向激动剂1'-甲基-5-[[2'-甲基-4'-(5-甲基-1,2,4-恶二唑-3-基)联苯-4-基]羰基]-2,3,6,7-四氢-螺[呋喃并[2,3-f]吲哚-3,4'-哌啶](SB-224289)在体外和体内均能有效阻断5-羟色胺（5-HT）终末自身受体功能。
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Antidepressant drugs inhibit a glial 5-hydroxytryptamine transporter in rat brain.抗抑郁药物抑制大鼠脑中的一种胶质细胞5-羟色胺转运体。
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Autoreceptor antagonists enhance the effect of the reuptake inhibitor citalopram on extracellular 5-HT: this effect persists after repeated citalopram treatment.自体受体拮抗剂可增强再摄取抑制剂西酞普兰对细胞外5-羟色胺（5-HT）的作用：重复使用西酞普兰治疗后，这种作用仍然存在。
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Effect of 5-HT1A receptor antagonists on citalopram-induced increase in extracellular serotonin in the frontal cortex, striatum and dorsal hippocampus.5-羟色胺1A受体拮抗剂对西酞普兰引起的额叶皮质、纹状体和背侧海马体细胞外5-羟色胺增加的影响。
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Effect of a selective 5-HT reuptake inhibitor in combination with 5-HT1A and 5-HT1B receptor antagonists on extracellular 5-HT in rat frontal cortex in vivo.一种选择性5-羟色胺再摄取抑制剂与5-羟色胺1A和5-羟色胺1B受体拮抗剂联合使用对大鼠额叶皮质细胞外5-羟色胺的体内影响。
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Preferential potentiation of the effects of serotonin uptake inhibitors by 5-HT1A receptor antagonists in the dorsal raphe pathway: role of somatodendritic autoreceptors.5-HT1A受体拮抗剂对中缝背核通路中血清素摄取抑制剂作用的优先增强：树突体自身受体的作用
J Neurochem. 1997 Jun;68(6):2593-603. doi: 10.1046/j.1471-4159.1997.68062593.x.
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