Cone Neurosurgical Research Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, 3801 University Street, Montreal, Quebec, Canada.
Nucl Med Biol. 2012 Oct;39(7):1053-7. doi: 10.1016/j.nucmedbio.2012.04.001. Epub 2012 May 5.
A considerable body of evidence indicates the involvement of the neurotransmitter serotonin (5-HT) in the pathogenesis and treatment of depression.
The acute effect of fluvoxamine, on 5-HT synthesis rates was investigated in rat brain regions, using α-(14)C-methyl-L-tryptophan as a tracer. Fluvoxamine (25 mg/kg) and saline (control) were injected intraperitoneally, one hour before the injection of the tracer (30 μCi).
There was no significant effect of fluvoxamine on plasma free tryptophan. After Benjamini-Hochberg False Discovery Rate correction, a significant decrease in the 5-HT synthesis rate in the fluvoxamine treated rats, was found in the raphe magnus (-32%), but not in the median (-14%) and dorsal (-3%) raphe nuclei. In the regions with serotonergic axon terminals, significant increases in synthesis rates were observed in the dorsal (+41%) and ventral (+43%) hippocampus, visual (+38%), auditory (+65%) and parietal (+37%) cortex, and the substantia nigra pars compacta (+56%). There were no significant changes in the 5-HT synthesis rates in the median (+11%) and lateral (+24%) part of the caudate-putamen, nucleus accumbens (+5%), VTA (+16%) or frontal cortex (+ 6%).
The data show that the acute administration of fluvoxamine affects 5-HT synthesis rates in a regionally specific pattern, with a general elevation of the synthesis in the terminal regions and a reduction in some cell body structures. The reasons for the regional specific effect of fluvoxamine on 5-HT synthesis are unclear, but may be mediated by the presynaptic serotonergic autoreceptors.
大量证据表明，神经递质 5-羟色胺（5-HT）参与了抑郁症的发病机制和治疗。
采用α-（14）C-甲基-L-色氨酸作为示踪剂，研究了氟伏沙明对大鼠脑区 5-HT 合成率的急性影响。氟伏沙明（25mg/kg）和生理盐水（对照）在示踪剂（30μCi）注射前 1 小时经腹腔注射。
氟伏沙明对血浆游离色氨酸没有显著影响。经过 Benjamini-Hochberg 假发现率校正后，发现氟伏沙明处理组大鼠中中缝大核（-32%）5-HT 合成率显著降低，但中缝核（-14%）和背侧中缝核（-3%）无显著降低。在有 5-HT 轴突末梢的区域，观察到背侧海马（+41%）、腹侧海马（+43%）、视皮层（+38%）、听皮层（+65%）和顶叶皮层（+37%）以及黑质致密部（+56%）的合成率显著增加。而在中脑尾壳核的中缝核（+11%）和外侧部（+24%）、伏隔核（+5%）、腹侧被盖区（VTA）（+16%）或额叶皮质（+6%）的 5-HT 合成率无显著变化。
研究数据表明，氟伏沙明的急性给药以区域特异性的方式影响 5-HT 合成率，在末梢区域普遍升高，而在一些细胞体结构中降低。氟伏沙明对 5-HT 合成的区域特异性影响的原因尚不清楚，但可能是通过突触前 5-HT 自身受体介导的。
