engleski

Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: an autoradiographic study

Introduction. A considerable body of evidence indicates the involvement of the neurotransmitter serotonin (5-HT) in the pathogenesis and treatment of depression. Methods. The acute effect of fluvoxamine, on 5-HT synthesis rates was investigated in rat brain regions, using α-14C-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). Results. There were no significant effect 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 %). Conclusions. 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.

autoradiography; fluvoxamine; serotonin synthesis; selective serotonin reuptake inhibitor; tracer method

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