EFFECT OF L-STEPHOLIDINE ON MONOAMINE METABOLISM IN RAT BRAIN

Effect of 1-stepholidine(SPD), a tetrahydroquinoline alkaloid and partial agonist of dopamine (DA) receptor, on monoamine metabolism in rat brain was studied using HPLC-electrochemical detector. The results indicate that at doses of 15-120 mg/kg the levels of DA metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were increased by 2-3 times in a dose-dependent manner in the striatum and limbic areas. The elevation of DOPAC and HVA levels reached its peak at 30 rain and lasted about 4 h or more after treatment. SPD was shown to deplete DA in the striatum and DA and NA in the limbic area. The data of increased DA metabolites support the notion that SPD is a DA receptor antagonist. It would be expected that post-synaptic receptor blockade by SPD will lead to a compensatory increase in DA turnover rate as witnessed by elevations in DOPAC and HVA, but normal levels of DA should remain unchanged. Therefore, depletion of DA and NA in the brain suggests that in addition to a receptor blocking effect, SPD is also involved in other process of neurotrasmission, i, e. inhibiting monoamine storage (granular effect) or reuptake. Increase in 5-HIAA levels in the striatum was also observed.