Reduction in serotonin synthesis following acute and chronic treatments with paroxetine, a selective serotonin reuptake inhibitor, in rat brain: an autoradiographic study with alpha-[14C]methyl-L-tryptophan(2).
Serotonin (5-HT) synthesis rates were calculated on the basis of the assumption that trapping of alpha-[14C]methyl-L-tryptophan (alpha-[14C]MTrp) is directly related to brain 5-HT synthesis. In the first series of experiments, an acute intraperitoneal injection of paroxetine (10 mg/kg) produced a significant reduction in 5-HT synthesis in brain structures containing serotonergic cell bodies (the dorsal, median, and pallidum raphe nuclei), as well as in most projection areas: the ventral tegmental area, median forebrain bundle, hippocampus CA3 region, and nigrostriatal structures (substantia nigra, lateral and medial caudate nuclei). The reductions in the projection areas were greater (between 25 and 53%) than in those areas containing serotonergic cell bodies (between 18 and 23%). In the cerebral cortex, 5-HT synthesis rates were not modified by acute paroxetine treatment. In a second series of experiments, rats were treated with paroxetine (10 mg/kg/day, s.c., delivered by osmotic minipumps) for 14 days. There was a marked decrease (39-69%) in 5-HT synthesis in every structure examined. In conclusion, the present data suggest that the effects of paroxetine on 5-HT synthesis in the cerebral cortex are different from its effects in the cell body area of the brainstem.
Yamane
F
F
Cone Laboratory for Neurosurgical Research, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University St., H3A 2B4, Montreal, Quebec, Canada.
Okazawa
H
H
Blier
P
P
Diksic
M
M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism*
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan; C493232:Slc6a4 protein, rat; C028129:tryptophan methyl ester