Effects of the trichothecene mycotoxin T-2 toxin on neurotransmitters and metabolites in discrete areas of the rat brain.
T-2 toxin has been shown to affect the central nervous system. Only recently have attempts been made to characterize the neurochemical perturbations associated with T-2 intoxication. To examine the effect of T-2 on regional brain biogenic monoamines and selected metabolites, male rats were dosed orally with T-2 toxin in corn oil at 0.1, 1.0 or 2.5 mg/kg body weight. At 2, 6 and 10 hr post-dosing, rats were killed, brains were collected and stored at -80 degrees until analysed. Brain nuclei, including nucleus raphe magnus, paraventricular nucleus, locus coeruleus, substantia nigra, medial forebrain bundle, nucleus accumbens and olfactory tubercle, were analysed. T-2 treatment increased 5-hydroxy-3-indoleacetic acid and serotonin throughout the brain, and produced a transient increase in norepinephrine in the nucleus raphe magnus and a temporary decrease in the substantia nigra. Regional dihydroxyphenylacetic acid concentration was affected, with increased DOPAC observed in the locus coeruleus, medial forebrain bundle and paraventricular nucleus of the hypothalamus, and decreased DOPAC in the olfactory tubercles. No regional changes in epinephrine or dopamine were observed. Few treatment differences were observed, with the 0.1 mg/kg body weight T-2, 2% of the LD50, significantly affecting brain monoamines. It had been suggested that neurological manifestations of T-2 toxin are the result of brain hypoxia; however, the altered brain monoamine profile observed at doses that do not alter heart function, suggests the brain is a primary site of trichothecene action.
Department of Foods and Nutrition, University of Manitoba, Winnipeg, Canada.
J
J
Wang
D W
DW
Fitzpatrick
J R
JR
Wilson
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D015306:Biogenic Monoamines / Q000032:analysis / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003314:Corn Oil; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000032:analysis / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000032:analysis / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000032:analysis / Q000378:metabolism; D013605:T-2 Toxin / Q000008:administration & dosage / Q000633:toxicity*
D015306:Biogenic Monoamines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003314:Corn Oil; D013605:T-2 Toxin; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine