Bosker F J, de Winter T Y, Klompmakers A A, Westenberg H G
Rudolf Magnus Institute for Neuroscience, Department of Psychiatry, University Hospital Utrecht, The Netherlands.
J Neurochem. 1996 Jun;66(6):2546-55. doi: 10.1046/j.1471-4159.1996.66062546.x.
The effects of systemic administration of the serotonin (5-hydroxytryptamine) 5-HT1A receptor agonists flesinoxan and 8-hydroxy-2-(di-n-propylamino)tetralin on extracellular 5-HT were measured using microdialysis probes in both median raphe nucleus and dorsal hippocampus. Both 5-HT1A agonists dose-dependently decreased dialysate 5-HT levels from both brain regions. The effects of flesinoxan in the median raphe (0.3 mg/kg) and dorsal hippocampus (1.0 mg/kg) could be blocked by the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexane carboxamide trihydrochloride (WAY 100,635) at a dose of 0.05 mg/kg s.c. The antagonist itself had no effect at this dosage. Local perfusion of flesinoxan for 30 min through the dialysis probe into the median raphe region at concentrations of 20, 100, and 1,000 nM resulted in a significant decrease in dialysate 5-HT content from both regions. The effect of 100 nM flesinoxan could be blocked by coperfusion of 1,000 nM WAY 100,635. The data indicate that flesinoxan is a potent 5-HT1A receptor agonist and also support the notion that somatodendritic 5-HT1A autoreceptors regulate both terminal and somatodendritic 5-HT release.
使用微透析探针测量了血清素（5-羟色胺）5-HT1A受体激动剂氟司洛辛和8-羟基-2-（二正丙基氨基）四氢萘经全身给药后对中缝核和背侧海马细胞外血清素的影响。两种5-HT1A激动剂均剂量依赖性地降低了这两个脑区的透析液血清素水平。氟司洛辛在中缝核（0.3mg/kg）和背侧海马（1.0mg/kg）的作用可被剂量为0.05mg/kg皮下注射的5-HT1A受体拮抗剂N-[2-[4-（2-甲氧基苯基）-1-哌嗪基]乙基]-N-（2-吡啶基）环己烷甲酰胺三盐酸盐（WAY 100,635）阻断。该拮抗剂在该剂量下本身无作用。通过透析探针以20、100和1000nM的浓度在中缝核区域局部灌注氟司洛辛30分钟，导致两个区域的透析液血清素含量显著降低。100nM氟司洛辛的作用可被1000nM WAY 100,635共同灌注阻断。数据表明氟司洛辛是一种有效的5-HT1A受体激动剂，也支持树突体5-HT1A自身受体调节终末和树突体5-HT释放的观点。
