Ferré S, Artigas F
Department of Neurochemistry, C.S.I.C., Barcelona, Spain.
Neurosci Lett. 1995 Feb 24;187(1):61-4. doi: 10.1016/0304-3940(95)11338-w.
By using brain microdialysis, clear differences in the effects of the systemic administration of clozapine and haloperidol on the extracellular concentration of dopamine (DA) and serotonin (5-HT) were found in the nucleus accumbens of freely moving rats. Haloperidol (0.5 mg/kg s.c.) significantly increased DA (ca. 40%) but did not modify 5-HT extracellular concentration, while clozapine (5 mg/kg s.c.) significantly decreased 5-HT (ca. 40%) but did not change DA concentration. Locally infused, clozapine (10(-5) M) significantly increased DA (75%) and reduced 5-HT extracellular concentration (50%). The reduction of 5-HT cannot be explained by a clozapine-induced blockade of DA receptors, because the local infusion (10(-5) M) of the DA D2-like antagonist raclopride and the DA D1-like antagonist SCH 23390 significantly increased DA (ca. 300% and 200%, respectively) but did not modify 5-HT extracellular concentration. Conversely, the DA D2-like agonist quinpirole and the DA D1-like agonist SKF-38393 significantly decreased (ca. 60% in both cases) DA extracellular concentration without affecting that of 5-HT. The present results indicate that clozapine displays a powerful anti-serotoninergic effect by inhibiting 5-HT release in the nucleus accumbens, an effect probably derived from the reduction of firing activity at the dorsal raphe and by local mechanisms that may involve some 5-HT receptor subtype(s).
通过使用脑微透析技术，发现在自由活动大鼠的伏隔核中，氯氮平和氟哌啶醇全身给药对细胞外多巴胺（DA）和5-羟色胺（5-HT）浓度的影响存在明显差异。氟哌啶醇（0.5毫克/千克，皮下注射）显著增加DA（约40%），但不改变5-HT细胞外浓度，而氯氮平（5毫克/千克，皮下注射）显著降低5-HT（约40%），但不改变DA浓度。局部注入氯氮平（10^-5摩尔）显著增加DA（75%）并降低5-HT细胞外浓度（50%）。5-HT的降低不能用氯氮平诱导的DA受体阻断来解释，因为局部注入DA D2样拮抗剂雷氯必利和DA D1样拮抗剂SCH 23390（10^-5摩尔）显著增加DA（分别约300%和200%），但不改变5-HT细胞外浓度。相反，DA D2样激动剂喹吡罗和DA D1样激动剂SKF-38393显著降低（两种情况均约60%）DA细胞外浓度，而不影响5-HT的浓度。目前的结果表明，氯氮平通过抑制伏隔核中5-HT的释放表现出强大的抗5-羟色胺能作用，这种作用可能源于背侧中缝核放电活动的减少以及可能涉及某些5-HT受体亚型的局部机制。
