1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline increases extracellular serotonin and stimulates hydroxyl radical production in rats.
1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo), a neurotoxin structurally similar to the dopaminergic neurotoxin MPTP, may be formed in humans treated with chloral hydrate or exposed to trichloroethylene, a widely used industrial solvent. Systemically administered TaClo (0.4 mg/kg, i.p.) induced an immediate and transient release of dopamine (DA) and serotonin (5-HT) measured using microdialysis. However, only 5-HT was increased significantly (area under the curve, AUC, for the 1-2 h-period following TaClo administration: 400% compared with the respective control value; 2-3 h-period: 326%). This was followed by a progressive increase in hydroxyl radical formation reflected by higher extracellular concentrations of the hydroxylate product of salicylic acid, 2,3-dihydroxybenzoic acid (AUC for the 1-2 h period following TaClo administration: 182% compared with the respective control value; 2-3 h period: 190%). In contrast, extracellular glutamate and GABA were increased 2-3 h post-injection by 64 and 51%, respectively. These data suggest that TaClo stimulates the generation of hydroxyl free radicals via an acute release of 5-HT and perhaps DA.
Gerlach
M
M
Department of Psychiatry, University of Würzburg, Germany.
Xiao
A Y
AY
Heim
C
C
Lan
J
J
God
R
R
Feineis
D
D
Bringmann
G
G
Riederer
P
P
Sontag
K H
KH
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002243:Carbolines / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D062385:Hydroxybenzoates / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002243:Carbolines; D062385:Hydroxybenzoates; D015102:3,4-Dihydroxyphenylacetic Acid; C067372:1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline; D001224:Aspartic Acid; D012701:Serotonin; D017665:Hydroxyl Radical; D018698:Glutamic Acid; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; C009135:2,3-dihydroxybenzoic acid; D004298:Dopamine; D006719:Homovanillic Acid