Effects of chronic administration of ondansetron (GR38032F), a selective 5-HT3 receptor antagonist, on monoamine metabolism in mesolimbic and nigrostriatal dopaminergic neurons and on striatal D2-receptor binding.
The effects of chronic administration of the selective 5-HT3 receptor antagonist ondansetron (GR38032F) on dopamine (DA) and 5-hydroxytryptamine (5-HT) metabolism in the major ascending dopaminergic neurons and on striatal D2-receptor binding characteristics were investigated. The metabolism of 5-HT was also studied in a number of other brain areas. Chronic ondansetron (0.2 mg/kg/day and 1.0 mg/kg/day SC for 16 days) did not change DA or 5-HT metabolism in the nigrostriatal or mesolimbic dopaminergic areas, although the larger dose of ondansetron slightly and statistically significantly reduced basal concentrations of DA and 5-HT in the nucleus caudatus. D2-receptor binding characteristics were not affected in the caudate-putamen. Ondansetron did not change 5-HT metabolism in the nucleus raphé dorsalis, amygdala, hippocampus or in habenula. It is concluded that chronic administration of ondansetron does not change DA or 5-HT metabolism in the major ascending dopaminergic neurons. This suggest that unlike chronic D2-receptor blockade, chronic blockade of central 5-HT3 receptors does not result in a similar reduction in the activity of nigrostriatal and mesolimbic dopaminergic neurons.
Koulu
M
M
Department of Pharmacology, University of Turku, Finland.
Lappalainen
J
J
Hietala
J
J
Sjöholm
B
B
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017294:Ondansetron; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D015306:Biogenic Monoamines; D007093:Imidazoles; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D017294:Ondansetron; D004298:Dopamine