Antidopaminergic effects of 1,2,3,4-tetrahydroisoquinoline and salsolinol

Immediate behavioral and biochemical effects of single doses of 1,2,3,4-tet rahydroisoquinoline (TIQ, 50 mg/kg) and salsolinol (100 mg/kg), suspected o f involvement in etiology of Parkinson's disease, were investigated. Apomor phine (0.25 mg/kg) or haloperidol (1 mg/kg) were administered to TIQ or sal solinol pretreated Wistar rats. In additional experiment the displacement o f [H-3]apomorphine by TIQ, salsolinol and dopamine receptor agonists and an tagonists was tested. Both tetrahydroisoquinolines only slightly affected b ehavior and dopamine metabolism in naive rats? but very effectively abolish ed the behavioral and biochemical effects of apomorphine (hyperactivity, de pression of striatal HVA level). The behavioral and biochemical effects of haloperidol were unchanged by administration of TIQ nor salsolinol. The tet rahydroisoquinolines displaced [H-3]apomorphine from its binding sites with effectiveness comparable to that of dopamine. The results support the hypo thesis that endogenous tetrahydroisoquinolines may play an important role i n regulation of dopaminergic activity in non-senescent organisms.