Effects of acute and chronic administration of the serotonin1A agonist buspirone on serotonin synthesis in the rat brain.
The effects of acute and chronic administration of buspirone, a serotonin 5-HT1A agonist, on the 5-HT synthesis rates in various rat brain structures were investigated using alpha-[14C]methyl-L-tryptophan (alpha-[14C]MTrp) and an autoradiographic method. In the acute treatment study, buspirone (10 mg/kg) was injected subcutaneously 30 min before alpha-[14C]MTrp administration (30 microCi over 2 min) into a femoral vein. In the chronic treatment study, buspirone was given in a sustained fashion (10 mg/kg/day) for 14 days using an osmotic minipump implanted subcutaneously. Rats were killed 60 and 150 min after alpha-[14C]MTrp administration (two-time point method). A single dose of buspirone induced a significant decrease of 5-HT synthesis throughout the brain with the exception of the pineal body. However, the chronic treatment with buspirone did not induce significant differences in 5-HT synthesis in the brain. There was no significant difference in plasma free tryptophan concentration between any of the groups. The unaltered 5-HT synthesis rates in the chronic treatment study likely reflect a normalization of this parameter due to a desensitization of 5-HT1A autoreceptors on the cell body of 5-HT neurons, which has been previously shown to occur following long-term treatment with 5-HT1A agonists.
Okazawa
H
H
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Quebec, Canada.
Yamane
F
F
Blier
P
P
Diksic
M
M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002065:Buspirone / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors; D014364:Tryptophan / Q000031:analogs & derivatives
D017366:Serotonin Receptor Agonists; C020774:alpha-methyltryptophan; D012701:Serotonin; D014364:Tryptophan; D002065:Buspirone