Progressive Neurodegeneration of the Dopaminergic system and Inhibition of the Complex I Induced by the Chloral-Derived Tetrahydro-β-Carboline TaClo

TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline) appears to be a neurotoxic drug able to induce a slow developing degeneration of dopamine neurons. This is indicated from measurements of the apomorphine-induced locomotor activity. These experiments were carried out on rats in an open field system several days and 9 months after the end of a period of a 7 week injection of 0.2mg/ kg TaClo i. p. The neurotoxic potency appears to be different from that of MPTP or MPP+. MPP+ produces symptoms in monkeys that very closely resemble those in humans suffering from Parkinson’s disease (PD), but severe symptoms develop very rapidly after administration of the toxic drug. The use of the drug MPP+, therefore, does not allow the study of the different stages of the slowly progressive illness of PD in man, as the time between injection of drug and symptoms is to rapid (see also Jenner et al., 1986; Mohanakumar et al., 1994). It is therefore desirable to develop animal models that mimic the slow progressive advance of PD with the late onset of the first typical symptoms. We are not aware that such a model exists.