Abstract
The effects of acute and chronic administration of WAY100635 and WAY100135, serotonin (5-HT) 1A antagonists, on 5-HT synthesis rates, calculated from the trapping of α-[ 14C]methyl- l-tryptophan (α-MTrp), were evaluated in the rat brain using autoradiography. In the acute treatment studies, WAY100635 (1 mg/kg) induced a significant increase in 5-HT synthesis in the median raphe nucleus and some nerve terminal structures (range between 18 and 53%), while WAY100135 (10 mg/kg) produced a significant decrease of synthesis, in the range between 16 and 33%, in the raphe magnus nucleus and several projection areas. The action of WAY100635 given acutely was likely a result of antagonist actions at the 5-HT 1A somato-dendritic autoreceptors. WAY100135 probably acted acutely as a partial agonist. In the chronic treatment studies, WAY100635 (1 mg/kg/day) and WAY100135 (10 mg/kg/day) were administered for 7 days as s.c. injections once a day. Chronic treatment with both compounds significantly reduced the rate of 5-HT synthesis in the nerve terminal structures and produced a significant increase in the raphe nuclei. These treatments did not have any effect on the plasma free or total tryptophan.
Published Version
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