5-Hydroxytryptophol and 5-hydroxyindoleacetic acid levels in rat brain: effects of various drugs affecting serotonergic transmitter mechanisms.
The effect of various pharmacological treatments on the levels of free and total 5-hydroxytryptophol (5-HTOL) and 5-hydroxyindoleacetic acid (5-HIAA) in rat brain were investigated using a gas chromatographic-mass spectrometric technique. The disappearance of 5-HTOL following monoamine oxidase (MAO) inhibition induced by pargyline was more rapid (t1/2 10-15 min) than that of 5-HIAA (t1/2 30-40 min) in all regions investigated, indicating a rapid turnover of 5-HTOL. The selective MAO-A inhibitor chlorgyline produced a more pronounced reduction of 5-HTOL than of 5-HIAA, while the MAO-B inhibitor deprenyl was without effect on both serotonin metabolites. The MAO-A inhibitor amiflamine which is selective for serotonin neurons, was also more effective in reducing free 5-HTOL levels than of 5-HIAA levels, suggesting that the formation of 5-HTOL is closely associated with serotonin neurons. Neonatal treatment with the serotonin neurotoxin 5, 7-dihydroxytryptamine (5,7-HT) led to a more pronounced reduction of 5-HTOL levels in cerebral cortex than that of 5-HIAA levels, while the increase of 5-HTOL levels in pons-medulla was more marked than of 5-HIAA levels. Probenecid treatment increased several fold both conjugated 5-HTOL and 5-HIAA levels in brain tissue. An increase was also noted for free 5-HTOL, although of less magnitude. Treatment with the serotonin receptor active agents methiothepin and d-lysergic acid diethylamide produced similar alterations of free 5-HTOL and 5-HIAA. The present results have demonstrated that free 5-HTOL has a rapid turnover in rat brain and that free 5-HTOL levels may serve as a useful index for serotonin turnover.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D006917:Hydroxytryptophol / Q000378:metabolism*; D007211:Indoles / Q000378:metabolism*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism*
D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; D006917:Hydroxytryptophol; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D008719:Methiothepin; D008238:Lysergic Acid Diethylamide; D011339:Probenecid