Mück-Seler D, Jevric-Causevic A, Diksic M
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
J Neurochem. 1996 Dec;67(6):2434-42. doi: 10.1046/j.1471-4159.1996.67062434.x.
The aim of the present study was to test the hypothesis that there should be a difference between the effects of an acute and an 8-day (chronic) administration of fluoxetine (10 mg/kg) on the rate of serotonin [5-hydroxytryptamine (5-HT)] synthesis. The 5-HT synthesis rate was measured in discrete regions of the rat brain using the alpha-[14C]methyl-L-tryptophan autoradiographic method. The results show that the acute and chronic fluoxetine treatments influence the 5-HT synthesis rate in different ways. A single dose of fluoxetine induced a significant increase in 5-HT synthesis in the visual, auditory, and parietal cortices, substantia nigra, hypothalamus, ventral thalamus, and dorsal hippocampus. In contrast, after a chronic treatment a decrease was observed in the substantia nigra, caudate, and nucleus accumbens, the auditory, parietal, sensorimotor, and frontal cortices, and ventral tegmental area. A significant decrease in the rate of 5-HT synthesis was observed in the dorsal raphe after both the single and chronic treatments. The results suggest that extracellular 5-HT has a delayed influence on the brain 5-HT synthesis rate in structures with serotonergic terminals. The findings from the acute study could be important for patients who have just started receiving fluoxetine treatment, as an increase in the 5-HT synthesis rate might occur in the acute phase of their treatment. In addition, the findings, from the chronic treatment study might give us a better understanding of how the brain serotonergic system adapts during a prolonged exposure to extracellular 5-HT.
急性和8天（慢性）给予氟西汀（10毫克/千克）对血清素[5-羟色胺（5-HT）]合成速率的影响存在差异。使用α-[14C]甲基-L-色氨酸放射自显影法在大鼠脑的离散区域测量5-HT合成速率。结果表明，急性和慢性氟西汀治疗以不同方式影响5-HT合成速率。单次给予氟西汀可使视觉、听觉和顶叶皮质、黑质、下丘脑、腹侧丘脑和背侧海马体中的5-HT合成显著增加。相比之下，慢性治疗后，黑质、尾状核、伏隔核、听觉、顶叶、感觉运动和额叶皮质以及腹侧被盖区的5-HT合成减少。单次和慢性治疗后，背侧中缝核中的5-HT合成速率均显著降低。结果表明，细胞外5-HT对具有5-羟色胺能终末的结构中的脑5-HT合成速率具有延迟影响。急性研究的结果对于刚开始接受氟西汀治疗的患者可能很重要，因为在其治疗的急性期可能会出现5-HT合成速率增加。此外，慢性治疗研究的结果可能会让我们更好地了解在长时间暴露于细胞外5-HT期间脑5-羟色胺能系统是如何适应的。
