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 s tructurally similar to the dopaminergic neurotoxin MPTP, may be formed in h umans treated with chloral hydrate or exposed to trichloroethylene, a widel y 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 sign ificantly (area under the curve, AUG, for the 1-2 h-period following TaClo administration: 400% compared with the respective control value; 2-3 h-peri od: 326%). This was followed by a progressive increase in hydroxyl radical formation reflected by higher extracellular concentrations of the hydroxyla te product of salicylic acid, 2,3-dihydroxybenzoic acid (AUC for the 1-2 h period following TaClo administration: 182% compared with the respective co ntrol value; 2-3 h period: 190%). In contrast, extracellular glutamate and GABA were increased 2-3 h postinjection 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. (C) 1998 Elsevier Science Ire land Ltd. All rights reserved.