Influence of repeated treatment with buspirone on central 5-hydroxytryptamine and dopamine synthesis.
The anxiolytic agent buspirone was administered subcutaneously twice a day for 10 days to Sprague-Dawley rats, at a dose of 3 mg kg-1. Controls were given saline. On the eleventh day, the rats were given an injection of NSD-1015, an aromatic L-amino acid decarboxylase inhibitor, 30 min before decapitation. To another group of rats, only one injection of buspirone was given, followed 30 min later by NSD-1015. After a further 30 min the animals were decapitated. The brains were rapidly removed and the raphe nuclei, striatum, hippocampus and cerebellum were dissected out on to dry ice. With the use of HPLC, the four regions of the brain were assayed for 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine, reflecting the synthesis of 5-HT and dopamine, respectively. In those rats which had received an acute dose of buspirone, the synthesis of 5-HT was substantially reduced in all four regions of the brain. However, in those rats which had received buspirone for 10 days, no such alterations in the synthesis of 5-HT were observed. The synthesis of dopamine was unchanged in any of the regions of the brain, after the acute dose of buspirone. After 10 days of treatment with buspirone, however, the synthesis of dopamine in the striatum was significantly reduced. These findings suggest that repeated treatment with buspirone reduces the synthesis of dopamine in the striatum but that the synthesis of 5-HT is unaffected.
Tunnicliff
G
G
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Evansville 47712.
Brokaw
J J
JJ
Hausz
J A
JA
Matheson
G K
GK
White
G W
GW
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001923:Brain Chemistry / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D006834:Hydrazines; D012701:Serotonin; D004295:Dihydroxyphenylalanine; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan; D002065:Buspirone; D004298:Dopamine