Biochemical lesions of the nigrostriatal system by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline) and derivatives

In vivo voltammetry with carbon fibre electrodes was used to study the effects of highly halogenated tetrahydro-beta-carbolines on the striatal dopamine (DA) metabolism of the rat. As representatives of chloral-derived heterocycles, ''TaClo'' (1-trichloro-1,2,3,4-tetrahydro-beta-carboline) and its N-methylated derivative. ''N-methyl-TaClo'', were investigated. After intranigral injection of 10 mu g TaClo, the DA activity in the ipsilateral striatum was reduced compared with the intact side. Application of N-methyl-TaClo (10 mu g) resulted in a nearly total reduction of the DOPAC signal. Furthermore, also ''TaBro'' (1-tribromomethyl-1,2,3,4-tetrahydro-beta-carboline), the bromal-derived analogue of TaClo, was tested. The impairment of the DA metabolism in rats achieved with 10 beta g TaBro was found to be between that observed after application of TaClo and N-methyl-TaClo, respectively. The results demonstrate the toxic potential of chloral- and bromal-derived beta-carbolines towards dopaminergic neurons.