Drug-induced alterations in the efflux of 5-hydroxytryptamine and of 5-hydroxyindoleacetic acid into superfusates of the rat spinal cord.
The effect of dl-p-chloroamphetamine, fluoxetine and probenecid on the efflux of endogenous 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid (5HIAA) into superfusates of the spinal cord of anesthetized rats was examined. Mean basal efflux of 5HT and 5HIAA was 0.27 and 15.56 ng/ml superfusate, respectively. The addition of dl-p-chloroamphetamine to the superfusate produced a dose-dependent increase in the efflux of 5HT into the superfusate, but did not increase the efflux of 5HIAA. Probenecid (200 mg/kg i.p.) increased the basal efflux of both 5HT and 5HIAA as compared to control values. When administered systemically, fluoxetine (10 mg/kg i.p. or s.c.) decreased the basal efflux of 5HIAA, but did not alter the basal efflux of 5HT as compared to control values. In contrast, when administered in the superfusate, fluoxetine produced a dose-dependent increase in the basal efflux of 5HT, but did not alter the basal efflux of 5HIAA. The release of 5HT produced by the addition of 2.5 X 10(-4) M dl-p-chloroamphetamine to the superfusate was not prevented in rats pretreated systemically with fluoxetine, although when administered in the superfusate fluoxetine inhibited the dl-p-chloroamphetamine-induced release of 5HT.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D008297:Male; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D010133:p-Chloroamphetamine / Q000494:pharmacology
D005473:Fluoxetine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D010133:p-Chloroamphetamine; D011339:Probenecid