Dawson L A, Nguyen H Q, Li P
Neuroscience Discovery Research, Wyeth, CN8000, Princeton, New Jersey, NJ 08543, USA.
Br J Pharmacol. 2000 May;130(1):23-6. doi: 10.1038/sj.bjp.0703288.
Although the 5-HT(6) receptor subtype was identified some 5 years ago, very little is known about its function within the brain. Here we demonstrate, for the first time, the neurochemical effects of a selective 5-HT(6) receptor ligand. Using in vivo microdialysis in the freely moving rat, we evaluated the effects of the selective 5-HT(6) receptor antagonist SB-271046 by simultaneous measurement of 5-hydroxytryptamine (5-HT), dopamine (DA), noradrenaline (NA), glutamate and aspartate from the striatum and frontal cortex. SB-271046 did not alter basal levels of 5-HT, DA and NA in either brain region. Similarly, there was no change basal levels of either of the excitatory amino acids within the striatum. In contrast, administration of SB-271046 (10 mg kg(-1) s.c.) produced a significant (P<0.05), tetrodotoxin-dependent, increase in extracellular levels of both glutamate and aspartate within the frontal cortex, reaching maximum values of 375.4+/-82.3 and 215. 3+/-62.1% of preinjection values, respectively.
尽管5-羟色胺（6）受体亚型大约在5年前就已被识别，但人们对其在大脑中的功能却知之甚少。在此，我们首次证明了一种选择性5-羟色胺（6）受体配体的神经化学效应。利用自由活动大鼠体内微透析技术，我们通过同时测量纹状体和额叶皮质中的5-羟色胺（5-HT）、多巴胺（DA）、去甲肾上腺素（NA）、谷氨酸和天冬氨酸，评估了选择性5-羟色胺（6）受体拮抗剂SB - 271046的作用。SB - 271046并未改变任一脑区中5-HT、DA和NA的基础水平。同样，纹状体内兴奋性氨基酸的基础水平也没有变化。相比之下，皮下注射SB - 271046（10 mg·kg⁻¹）会使额叶皮质中谷氨酸和天冬氨酸的细胞外水平显著（P<0.05）且依赖于河豚毒素地升高，分别达到注射前水平的375.4±82.3%和215.3±62.1%的最大值。
