Neurochemical changes induced by acute and chronic administration of 1,2,3,4-tetrahydroisoquinoline and salsolinol in dopaminergic structures of rat brain

The finding that endogenous tetrahydroisoquinolines may be involved in the etiology of Parkinson's disease suggests that their administration may caus e changes resembling those observed in parkinsonian brain. We tested, using a high-performance liquid chromatography method, how single and chronic ad ministration of 1,2,3,4-tetrahydroisoquinoline and salsolinol affects dopam ine and serotonin metabolism in the neurons of extrapyramidal and mesolimbi c dopaminergic systems. We report that chronic administration of tetrahydro isoquinoline and salsolinol causes a decrease in a dopamine metabolism: the effect of tetrahydroisoquinoline was limited to the striatum, while salsol inol caused also a dramatic decline of dopamine level in the substantia nig ra. The effect of both compounds on serotonin metabolism was small or absen t. The tetrahydroisoquinolines produced no changes in the nucleus accumbens . The results indicate that tetrahydroisoquinoline and salsolinol specificall y affect the nigrostriatal dopamine system, but only when administered chro nically, and thus are compatible with the view that endogenous tetrahydrois oquinolines may participate in pathogenesis of Parkinson's disease. (C) 200 0 IBRO. Published by Elsevier Science Ltd.