De Deurwaerdère P, Stinus L, Spampinato U
Institut National de la Santé et de la Recherche Médicale Unité 259, Unité Mixte de Recherche-Centre National de la Recherche Scientifique 5541, Université Victor Ségalen Bordeaux 2, 33077 Bordeaux Cedex, France.
J Neurosci. 1998 Aug 15;18(16):6528-38. doi: 10.1523/JNEUROSCI.18-16-06528.1998.
In the present study we investigate, using in vivo microdialysis, the involvement of central 5-HT3 receptors in the effect of dorsal raphe nucleus (DRN) electrical stimulation on dopamine (DA), 3, 4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindole-3-acetic acid (5-HIAA) extracellular levels monitored in the nucleus accumbens and the striatum of halothane-anesthetized rats. DRN stimulation (300 microA, 1 msec at 3, 5, 10, and 20 Hz for 15 min) induced a frequency-dependent increase of accumbal DA release and a concomitant reduction of DA release in the ipsilateral striatum at 20 Hz. In both structures DOPAC and 5-HIAA dialysate contents were enhanced in a frequency-dependent manner. Central serotonin (5-HT) depletion, induced by intra-raphe injections of 5, 7-dihydroxytryptamine neurotoxin, abolished the effect of 20 Hz DRN stimulation on DA, DOPAC, and 5-HIAA extracellular levels in both regions. The 5-HT synthesis inhibitor para-chlorophenylalanine (3 x 400 mg/kg, i.p., for 3 d), although preventing the effect on DA release, failed to modify significantly the effect of 20 Hz DRN stimulation on DOPAC and 5-HIAA outflow in both structures. Ondansetron (0.1 and 1 mg/kg) and (S)-zacopride (0.1 mg/kg), two 5-HT3 antagonists, significantly impaired the increase of accumbal DA release induced by 20 Hz DRN stimulation but did not affect either the decrease of striatal DA release or the increase in DOPAC outflow in both structures. These results indicate that an enhancement of central 5-HT transmission induced by DRN stimulation differentially affects striatal and accumbal DA release and that endogenous 5-HT, via its action on 5-HT3 receptors, exerts a facilitatory control restricted to the mesoaccumbal DA pathway.
在本研究中，我们采用体内微透析技术，研究中脑5-羟色胺3（5-HT3）受体在背侧缝际核（DRN）电刺激对氟烷麻醉大鼠伏隔核和纹状体中多巴胺（DA）、3,4-二羟基苯乙酸（DOPAC）以及5-羟吲哚-3-乙酸（5-HIAA）细胞外水平影响中的作用。DRN刺激（300微安，1毫秒，频率为3、5、10和20赫兹，持续15分钟）可诱导伏隔核DA释放呈频率依赖性增加，并且在20赫兹时同侧纹状体中DA释放随之减少。在这两个结构中，DOPAC和5-HIAA的透析液含量均呈频率依赖性增加。通过向缝际核内注射5,7-二羟基色胺神经毒素诱导的中枢5-羟色胺（5-HT）耗竭，消除了20赫兹DRN刺激对这两个区域中DA、DOPAC和5-HIAA细胞外水平的影响。5-HT合成抑制剂对氯苯丙氨酸（3×400毫克/千克，腹腔注射，共3天）虽然可阻止对DA释放的影响，但未能显著改变20赫兹DRN刺激对这两个结构中DOPAC和5-HIAA流出的影响。两种5-HT3拮抗剂昂丹司琼（0.1和1毫克/千克）和（S）-扎考必利（0.1毫克/千克）可显著削弱20赫兹DRN刺激诱导的伏隔核DA释放增加，但不影响纹状体DA释放的减少或这两个结构中DOPAC流出的增加。这些结果表明，DRN刺激诱导的中枢5-HT传递增强对纹状体和伏隔核DA释放有不同影响，并且内源性5-HT通过其对5-HT3受体的作用，仅对中脑-伏隔核DA通路发挥促进性调控作用。
