Fujii T, Yoshizawa M, Nakai K, Fujimoto K, Suzuki T, Kawashima K
Department of Pharmacology, Kyoritsu College of Pharmacy, Minato-ku, Tokyo, Japan.
Brain Res. 1997 Jul 4;761(2):244-9. doi: 10.1016/s0006-8993(97)00325-9.
The role of the serotonin (5-HT)1A receptor in the regulation of acetylcholine (ACh) release in the hippocampus was investigated using an in vivo microdialysis technique and a sensitive radioimmunoassay specific for ACh. The mean (+/- S.E.M.) basal ACh contents in the hippocampal perfusate of conscious, freely moving rats was 60 +/- 4 (n = 29) and 3691 +/- 265 fmol/30 min (n = 31), respectively, in the absence and presence of physostigmine (Phy) in the perfusion fluid. Systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.5 mg/kg, s.c.), a 5-HT1A agonist, significantly enhanced ACh release both in the presence and absence of Phy. Local application of 8-OH-DPAT (3-30 microM) into the hippocampus through the microdialysis probe significantly potentiated ACh release only in the presence of Phy, whereas no significant effect was observed in its absence. Pretreatment with NAN-190 (3 mg/kg, i.p.), a 5-HT1A antagonist, eliminated the increasing effect of systemically applied 8-OH-DPAT on ACh release, while NAN-190 alone had no effect on basal ACh release either in the absence or presence of Phy. Consistent with the time course of ACh release, systemic administration of 8-OH-DPAT evoked hyperlocomotion, which was reversed by NAN-190. However, local hippocampal application of 8-OH-DPAT did not affect the locomotor activity of the rats. These findings suggest that at least two different sites are involved in the 8-OH-DPAT-induced increase in the release of ACh in the rat hippocampus in vivo.
利用体内微透析技术和一种对乙酰胆碱（ACh）特异的灵敏放射免疫分析法，研究了5-羟色胺（5-HT）1A受体在调节海马中乙酰胆碱释放方面的作用。在灌注液中不存在和存在毒扁豆碱（Phy）的情况下，清醒、自由活动大鼠海马灌流液中乙酰胆碱的平均（±标准误）基础含量分别为60±4（n = 29）和3691±265 fmol/30分钟（n = 31）。5-HT1A激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT，0.5毫克/千克，皮下注射）的全身给药，在存在和不存在Phy的情况下均显著增强了乙酰胆碱的释放。通过微透析探针将8-OH-DPAT（3 - 30微摩尔）局部应用于海马，仅在存在Phy时显著增强了乙酰胆碱的释放，而在不存在Phy时未观察到显著影响。5-HT1A拮抗剂NAN-190（3毫克/千克，腹腔注射）预处理消除了全身应用8-OH-DPAT对乙酰胆碱释放的增强作用，而单独的NAN-190在不存在或存在Phy的情况下对基础乙酰胆碱释放均无影响。与乙酰胆碱释放的时间进程一致，全身应用8-OH-DPAT引起了运动亢进，这被NAN-190逆转。然而，海马局部应用8-OH-DPAT并不影响大鼠的运动活动。这些发现表明，在体内8-OH-DPAT诱导的大鼠海马乙酰胆碱释放增加中至少涉及两个不同的部位。
