title: Effect of the beta-adrenoceptor agonist flerobuterol on serotonin synthesis in the rat brain.
abstract: The influence of 2- and 14-day treatments with flerobuterol, a preferential beta(2)-adrenoceptor agonist, on regional serotonin (5-HT) synthesis in the rat brain was studied by autoradiography using alpha-[(14)C]methyl-L-tryptophan. Flerobuterol was delivered at a rate of 0.5 mg/kg/day using osmotic pumps implanted s.c. The 2-day flerobuterol treatment significantly increased plasma Trp, both free and total, and decreased plasma Leu and Ile. This resulted in a significant increase in the facilitated transport of Trp. There was a significant increase in the synthesis of 5-HT in the 2-day treatment group in the dorsal and median raphe as well as in all postsynaptic structures, with the exception of the hypothalamus. In contrast, after a 14-day treatment, the enhanced facilitated transport of Trp was no longer present, and the increase in the rate of 5-HT synthesis persisted only in the parietal and occipital cortex and the superior colliculus. These data suggest that flerobuterol, similar to other beta-adrenergic agonists, acutely increases 5-HT synthesis, in part, through an elevation of brain Trp availability.
authors.affiliation: Cone Laboratory for Neurosurgical Research, Department of Neurology and Neurosurgery, and Montreal Neurological Institute, McGill University, Montreal, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Tsuiki
authors.forename: P
authors.initials: P
authors.lastname: Blier
authors.forename: M
authors.initials: M
authors.lastname: Diksic
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis*
chemical_list: D000318:Adrenergic beta-Agonists; D012701:Serotonin; C071321:flerobuterol; D000420:Albuterol