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

Abstract

Immediate behavioral and biochemical effects of single doses of 1,2,3,4-tetrahydroisoquinoline (TIQ, 50 mg/kg) and salsolinol (100 mg/kg), suspected of involvement in etiology of Parkinson's disease, were investigated. Apomorphine (0.25 mg/kg) or haloperidol (1 mg/kg) were administered to TIQ or salsolinol pretreated Wistar rats. In additional experiment the displacement of [3H]apomorphine by TIQ, salsolinol and dopamine receptor agonists and antagonists was tested. Both tetrahydroisoquinolines only slightly affected behavior and dopamine metabolism in naive rats, but very effectively abolished the behavioral and biochemical effects of apomorphine (hyperactivity, depression of striatal HVA level). The behavioral and biochemical effects of haloperidol were unchanged by administration of TIQ nor salsolinol. The tetrahydroisoquinolines displaced [3H]apomorphine from its binding sites with effectiveness comparable to that of dopamine. The results support the hypothesis that endogenous tetrahydroisoquinolines may play an important role in regulation of dopaminergic activity in non-senescent organisms.