Naslov
Acute effect of fluvoxamine on the serotonin synthesis rate in rat brain areas innervated by dorsal and median raphe nuclei: an autoradiographic study

Autori
Muck-Šeler, Dorotea ; Pivac, Nela ; Diksic, Mirko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
The International Journal of Neuropsychopharmacology, Vol. 3, Supplement 1 / Mendlewicz, J ; Souery, D. - Brisel : Cambridge University Press, 2000

Skup
XXIInd Collegium Internationale Neuro-Psychopharmacologicum

Mjesto i datum
Bruxelles, Belgija, 09.07.2000. - 13.07.2000

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
serotonin synthesis rate; rat brain regions; fluvoxamine; autoradiography

Sažetak
A considerable body of evidence points to the involvement of neurotransmitter serotonin (5-HT) in the pathogenesis and treatment of depression. The present study was undertaken to gain further insight into relationship between serotonergic system and the mechanism of action of antidepressants. The acute effect of fluvoxamine (antidepressant, a selective 5-HT reuptake inhibitor), on the 5-HT synthesis rate was investigated in the rat brain regions, using the ŕ-14C-methyl-L-tryptophan (specific activity 55 mCi/mmol) as a tracer in an autoradiograpic method (Diksic et al., 1990). Fluvoxamine (25 mg/kg) and saline (control) were injected intraperitoneally, one hours before injection of tracer (30 ćCi). There were no changes in the concentrations of plasma free tryptophan in fluvoxamine and saline-treated rats. In the areas of serotonergic cell bodies the decrease in 5-HT synthesis rate in fluvoxamine treated rats, calculated as a percent (%) of the synthesis rate in the control group was -32% in magnus and -20% in median raphe nuclei (MRN), while a nonsignificant change in 5-HT synthesis rate was observed in the dorsal raphe nuclei (DRN) (-3%). It the areas of nerve terminals a pronounced increase in synthesis rate was observed in dorsal hippocampus (+41%), region receiving a preferential MRN innervation (Steinbusch, 1981). There were no changes in synthesis rate in median (-12%) and lateral (-23%) part of caudatus-putamen, nucleus accumbens (-4%), VTA (-15%) and frontal cortex (-7%), the areas of nerve terminals reported to receive 5-HT projections mostly from the DRN. In the majority of the rat brain structures receiving mixed DRN/MRN inputs the rate of 5-HT synthesis was significantly increased: sensory-motor (+36%), parietal (+37%), visual (+38%) and auditory (+65%) cortex, medial geniculate body (+48%), substantia nigra pars compacta (+56 %), ventral hippocampus (43%), and superior colliculus (+38%). The decrease in 5-HT synthesis was observed only in the region of medial forebrain bundle (-20%). The preliminary results shown that acute administration of fluvoxamine effects 5-HT synthesis rate in the regionally specific pattern. Supported by the MRC of Canada (MT13368), US Public service (RO1-NS29629) and Croatian Ministry of Science. -Diksic,M., Nagahiro, S., Sourkes, T.L.and Yamamoto, Y.L. A new method to measure brain serotonin synthesis in vivo.I. Theory and basic data for a biological model, J.Cereb. Blood Flow Metab.,10:1-12 (1990). -Steinbusch, H.W.M. Distribution of serotonin-immunoreactivity in the central nervous system of the rat cell bodies and terminals. Neuroscience, 6:557-618, 1981.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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