Effect of fluoxetine pretreatment on the neurochemical changes induced by amfonelic acid combined with spiperone in rats.
Combined treatment with amfonelic acid plus spiperone caused large increases in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and a decrease in dopamine in rat striatum. 5-Hydroxytryptamine (5-HT) was decreased in striatum (but not in hypothalamus), and 5-hydroxyindoleacetic acid (5-HIAA) was increased in the striatum. Pretreatment with fluoxetine, an inhibitor of uptake into 5-HT neurons, antagonized the decrease in 5-HT and the increase in 5-HIAA and in the ratio 5-HIAA/5-HT but did not antagonize the changes in dopamine or its metabolites. The amfonelic acid-spiperone combination apparently causes increased release of dopamine in striatum, and the released dopamine is accumulated by 5-HT nerve terminals via the membrane uptake carrier. Inhibition of that carrier by fluoxetine prevents the release of 5-HT caused by the dopamine influx.
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D005473:Fluoxetine / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009268:Nalidixic Acid / Q000031:analogs & derivatives; D009287:Naphthyridines / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013134:Spiperone / Q000494:pharmacology*
D009287:Naphthyridines; D011437:Propylamines; D005473:Fluoxetine; D012701:Serotonin; D009268:Nalidixic Acid; D013134:Spiperone; D006897:Hydroxyindoleacetic Acid; C006486:amfonelic acid; D004298:Dopamine