Biogenic amines as biomarkers for neurotoxicity.
There has been a surge of interest over the past several years in the use of neurochemical endpoints to contribute to our understanding of the mechanism of action of neurotoxicants. In our present presentation, two biogenic amine systems were selected as examples of biomarkers for neurotoxicity. To investigate these neurochemical endpoints, two prototype neurotoxicants were evaluated in experimental animals. One agent, reserpine, was used to assess developmental neurotoxicity and administered prenatally, while the other, MDMA, was used in the adult animal. The neurochemical biomarkers measured were dopamine, serotonin, and their metabolite (DOPAC and 5-HIAA) concentrations by HPLC/EC and dopamine receptor binding by radioligand receptor techniques. A review of the background, experimental design, and results are presented in this article. Our findings indicate that components of the biogenic amine systems can be used as sensitive neurochemical biomarkers of neurotoxicity. These neurochemical biomarkers can be correlated with neuropathological and behavioral biomarkers to aid in the understanding of mechanisms of neurotoxicity.
Ali
S F
SF
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079-9502.
Chang
L W
LW
Slikker
W
W
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000633:toxicity; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D015415:Biomarkers; D005260:Female; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009420:Nervous System / Q000187:drug effects* / Q000378:metabolism; D012110:Reserpine / Q000633:toxicity
D001679:Biogenic Amines; D015415:Biomarkers; D015104:3,4-Methylenedioxyamphetamine; D012110:Reserpine; D018817:N-Methyl-3,4-methylenedioxyamphetamine