Effect of midbrain raphé lesions or intracisternal 6-hydroxydopamine administration on D, L-5-hydroxytryptophan-14C metabolism after peripheral decarboxylase inhibition.
Brain and blood 14C-5-hydroxyindole metabolism was studied in normal, raphé-lesioned and 6-hydroxydopamine (60HDA)-treated rats given L-(-)-alpha-hydrazino-3, 4-dihydroxy-alpha-methylhydrocinnamic acid (MK-486) (50 mg/kg) intraperitoneally and 5-hydroxytryptophan (5-HTP)-14C (5 muCi, 0.51 mCi/mmol) intravenously. Raphé lesioning and 60HDA treatment caused significant decrements in brain 5-hydroxytryptamine (5-HT)-14C and 5-hydroxyindoleacetic acid (5-HIAA)-14C levels and 5-HT concentrations compared to those in normal controls. In normal and 60HDA-treated rats there were decreased brain dopamine levels, possibly a consequence of non-specific metabolism of 5-HTP in brain. Blood 5-HIAA-14C levels were significantly decreased in 60HDA-treated but not raphé-lesioned rats. As increased brain 5-HT turnover was observed in raphé-lesioned rats, this may have prevented a decrease in blood 5-HIAA-14C levels. The results suggest that changes in blood 5-HIAA-14C following MK-486 and 5-HTP-14C may be related to changes in brain 5-HT-14C metabolism.
D006916:5-Hydroxytryptophan / Q000378:metabolism*; D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D004298:Dopamine / Q000378:metabolism; D006892:Hydroxydopamines / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats
D006892:Hydroxydopamines; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D002262:Carboxy-Lyases; D004298:Dopamine; D009638:Norepinephrine