Lucas G, Di Matteo V, De Deurwaerdère P, Porras G, Martín-Ruiz R, Artigas F, Esposito E, Spampinato U
Laboratoire Neuropsychobiologie des Désadaptations, UMR-CNRS 5541, Université Victor Segalen Bordeaux 2, B.P. 31, 146 rue Léo-Saignat, 33077 Bordeaux Cedex, France.
Eur J Neurosci. 2001 Mar;13(5):889-98. doi: 10.1046/j.0953-816x.2000.01453.x.
In this study we investigated, using in vivo microdialysis and single unit recordings, the role of serotonin4 (5-HT4) receptors in the control of nigrostriatal and mesoaccumbal dopaminergic (DA) pathway activity. In freely moving rats, the 5-HT4 antagonist GR 125487 (1 mg/kg, i.p.), without effect on its own, significantly reduced the enhancement of striatal DA outflow induced by 0.01 (-35%) and 0.1 (-66%), but not 1 mg/kg, s.c. haloperidol (HAL). Intrastriatal infusion of GR 125487 (1 microM) had no influence on basal DA outflow, but attenuated (-49%) the effect of 0.01 mg/kg HAL. Systemic administration of GR 125487 modified neither basal nor 0.01 mg/kg HAL-stimulated accumbal DA outflow. In halothane-anaesthetized rats, 1 or 10 mg/kg GR 125487, without effect by itself, failed to modify the changes in accumbal and striatal DA outflow elicited by electrical stimulation (300 microA, 1 ms, 20 Hz, 15 min) of the dorsal raphe nucleus. Finally, GR 125487 (444 microg/kg, i.v.), whilst not affecting basal firing of DA neurons within either the substantia nigra or the ventral tegmental area, reduced HAL-stimulated (1--300 microg/kg, i.v.) impulse flow of nigrostriatal DA neurons only. These results indicate that 5-HT4 receptors exert a facilitatory control on both striatal DA release and nigral DA neuron impulse flow only when nigrostriatal DA transmission is under activated conditions. Furthermore, they indicate that the striatum constitutes a major site for the expression of the control exerted by 5-HT4 receptors on DA release. In contrast, 5-HT4 receptors have no influence on mesoaccumbal DA activity in either basal or activated conditions.
在本研究中，我们采用体内微透析和单细胞记录技术，研究了5-羟色胺4（5-HT4）受体在黑质纹状体和中脑伏隔核多巴胺能（DA）通路活动控制中的作用。在自由活动的大鼠中，5-HT4拮抗剂GR 125487（1毫克/千克，腹腔注射）单独使用时无作用，但能显著降低皮下注射0.01（-35%）和0.1（-66%）毫克/千克氟哌啶醇（HAL）所诱导的纹状体DA流出增强，但对1毫克/千克的HAL无此作用。纹状体内注射GR 125487（1微摩尔）对基础DA流出无影响，但减弱了（-49%）0.01毫克/千克HAL的作用。GR 125487的全身给药对基础的或0.01毫克/千克HAL刺激的伏隔核DA流出均无影响。在氟烷麻醉的大鼠中，1或10毫克/千克的GR 125487单独使用时无作用，未能改变电刺激（300微安，1毫秒，20赫兹，15分钟）中缝背核所引起的伏隔核和纹状体DA流出的变化。最后，GR 125487（444微克/千克，静脉注射）虽然不影响黑质或腹侧被盖区内DA神经元的基础放电，但仅降低了HAL刺激（1-300微克/千克，静脉注射）的黑质纹状体DA神经元的冲动发放。这些结果表明，仅当黑质纹状体DA传递处于激活状态时，5-HT4受体才对纹状体DA释放和黑质DA神经元冲动发放发挥促进性控制作用。此外，这些结果表明，纹状体是5-HT4受体对DA释放发挥控制作用的主要表达部位。相反，在基础或激活状态下，5-HT4受体对中脑伏隔核DA活动均无影响。
