Differential effects of L-trytophan and buspirone on biogenic amine contents and metabolism in Lurcher mice cerebellum.
The effects of serotoninergic stimulation on monoamines were studied in the heterozygous Lurcher (Lc/+) mutant mouse, a model of human cerebellar ataxia. Wild type (+/+) and Lc/+ mice were treated for 40 days with L-tryptophan or buspirone, and serotonin (5-HT), dopamine (DA), noradrenaline (NA) and their main metabolites were measured in the cerebellum. In +/+ mice, only buspirone increased concentrations of 5-HT metabolites. In the hypoplastic Lc/+ cerebellum, indoleamines were higher, and increased further after both treatments. The 5-HT turnover index was increased in +/+ mice by buspirone, while in Lc/+ mutants it increased after L-tryptophan but was decreased by buspirone, indicating that in the mutants nerve terminals synthesize and accumulate 5-HT, but may not utilize it efficiently. Catecholamine contents remained unchanged in +/+ mice, but in Lc/+ mutants with higher endogenous NA, L-tryptophan further increased NA and 3,4-dihydroxy-phenylacetic acid (DOPAC), and buspirone augmented NA, DA and DOPAC levels.
Reader
T A
TA
Centre de Recherche en Sciences Neurologiques, Faculté de Médecine, Université de Montréal, Montréal, Canada. tomas.a.reader@umontreal.ca
Ase
A R
AR
Le Marec
N
N
Lalonde
R
R
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D002065:Buspirone / Q000494:pharmacology*; D002524:Cerebellar Ataxia / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000494:pharmacology*
D001679:Biogenic Amines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D002065:Buspirone; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid