Gudelsky G A, Nash J F
Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio, USA.
J Neurochem. 1996 Jan;66(1):243-9. doi: 10.1046/j.1471-4159.1996.66010243.x.
In vivo microdialysis was used to determine whether the 3,4-methylenedioxymethamphetamine (MDMA)-induced release of serotonin (5-HT) in vivo involves a carrier-mediated process and to investigate further the state-dependent interaction between 5-HT and dopamine. MDMA produced a dose-dependent increase in the extracellular concentration of 5-HT in the striatum and prefrontal cortex that was attenuated by treatment with fluoxetine but not by tetrodotoxin. Suppression by fluoxetine of the MDMA-induced release of 5-HT was accompanied by a suppression of the MDMA-induced release of dopamine. Administration of MDMA to rats treated with carbidopa and L-5-hydroxytryptophan resulted in a synergistic elevation of the extracellular concentration of 5-HT that was much greater than that produced by either treatment alone. The MDMA-induced release of dopamine by MDMA also was potentiated in 5-hydroxytryptophan-treated rats. These data are consistent with the view that MDMA increases the extracellular concentration of 5-HT by facilitating carrier-mediated 5-HT release, which can be enhanced greatly under conditions in which 5-HT synthesis is stimulated. Moreover, these data are supportive of a state-dependent, stimulatory role of 5-HT in the regulation of dopamine release.
采用体内微透析技术来确定3,4-亚甲基二氧甲基苯丙胺（摇头丸）在体内诱导的5-羟色胺（5-HT）释放是否涉及载体介导的过程，并进一步研究5-HT与多巴胺之间的状态依赖性相互作用。摇头丸使纹状体和前额叶皮质中5-HT的细胞外浓度呈剂量依赖性增加，这种增加可被氟西汀治疗减弱，但不能被河豚毒素减弱。氟西汀对摇头丸诱导的5-HT释放的抑制作用伴随着对摇头丸诱导的多巴胺释放的抑制。给用卡比多巴和L-5-羟色氨酸治疗的大鼠施用摇头丸，导致5-HT的细胞外浓度协同升高，其升高幅度远大于单独使用任何一种治疗所产生的升高幅度。在5-羟色氨酸治疗的大鼠中，摇头丸诱导的多巴胺释放也增强。这些数据与以下观点一致，即摇头丸通过促进载体介导的5-HT释放来增加5-HT的细胞外浓度，在5-HT合成受到刺激的条件下，这种释放可大大增强。此外，这些数据支持5-HT在调节多巴胺释放中具有状态依赖性的刺激作用。
