Evaluation of acrylamide treatment on levels of major brain biogenic amines, their turnover rates, and metabolites.
Acrylamide, a widely used and chemically active substance, has caused delayed distal neuropathy in man and in experimental animals. Male rats administered 50 mg/kg/day acrylamide for 5 days demonstrated ataxia in preliminary rotorod experiments. Additional groups of rats were dosed with 5, 15 or 50 mg/kg/day acrylamide for 5 days, then sacrificed on day 6 at various time intervals after iv injections of tritiated tyrosine (Tyr) or tryptophan (Trp). Brain levels of Tyr, Trp, norepinephrine (NE), dopamine (DA), serotonin (5-HT), and respective metabolites, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MOPEG-sulfate), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) were assayed fluorometrically. Turnover rates of NE, DA and 5-HT were estimated by evaluating the rates of specific activity changes in neurotransmitters and precursor amino acids over time. A slight reduction of whole brain NE content was observed in rats administered 50 mg/kg/day acrylamide. Other neurotransmitter levels were not affected by acrylamide levels administered, nor were turnover rates affected. Levels of MOPEG-sulfate and DOPAC were unchanged at any dose tested. Increased levels of 5-HIAA were observed in rats receiving 15 and 50 mg/kg/day acrylamide. Results suggest that acrylamide neurotoxicity does not entail widespread damage to the neurons associated with these biogenic amines; however, the acid metabolite efflux from brain was significantly inhibited.
D020106:Acrylamide; D000178:Acrylamides / Q000494:pharmacology*; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000096:biosynthesis; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism
D000178:Acrylamides; D001679:Biogenic Amines; D002395:Catecholamines; D020106:Acrylamide; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine