Acute and chronic D-fenfluramine treatments have different effects on serotonin synthesis rates in the rat brain: an autoradiographic study.
The effects of acute and chronic treatments with D-fenfluramine on the regional rates of serotonin (5-hydroxy-tryptamine; 5-HT) synthesis were investigated using the alpha-[14C]methyl-L-tryptophan (alpha-[14C]MTrp) autoradiographic method. In the first series of experiments, acute D-fenfluramine treatment (5 mg/kg; i.p.) given 20 min before the tracer injection significantly (p<0.05) decreased 5-HT synthesis in the dorsal raphe, and significantly (p<0.05) increased the rates in the cerebral cortices and caudate nucleus, when compared to the rates in the control rats (saline treated). In a second series of experiments, following a 7-day treatment with D-fenfluramine (5 mg/kg/day; i.p.), a significant (p<0.05) decrease of 5-HT synthesis, in the dorsal raphe was observed, and significant (p<0.05) increases were observed in the hypothalamus, the dorsal thalamus, the medial and lateral geniculate body and some brain stem regions (locus ceruleus, inferior and superior colliculus). No significant changes were observed in the cerebral cortices.
Yamane
F
F
Cone Laboratory for Neurosurgical Research, Montreal Neurological Institute, McGill University, Quebec, Canada.
Tohyama
Y
Y
Diksic
M
M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004334:Drug Administration Schedule; D005277:Fenfluramine / Q000494:pharmacology*; D008297:Male; D009928:Organ Specificity; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012701:Serotonin / Q000096:biosynthesis*; D014364:Tryptophan / Q000378:metabolism*
D002250:Carbon Radioisotopes; D005277:Fenfluramine; D012701:Serotonin; D014364:Tryptophan