title: Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: an autoradiographic study.
abstract: BACKGROUND
  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-(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).
  
  
  RESULTS
  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%).
  
  
  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.
authors.affiliation: Cone Neurosurgical Research Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, 3801 University Street, Montreal, Quebec, Canada.
authors.forename: Dorotea
authors.initials: D
authors.lastname: Muck-Seler
authors.forename: Nela
authors.initials: N
authors.lastname: Pivac
authors.forename: Mirko
authors.initials: M
authors.lastname: Diksic
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D016666:Fluvoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis*; D013997:Time Factors
chemical_list: D012701:Serotonin; D016666:Fluvoxamine