Differential inhibitory effects of ascorbic acid on the binding of dopamine agonists and antagonists to neostriatal membrane preparations: correlations with behavioral effects

Abstract

Ascorbic acid was a potent inhibitor of the binding of both dopamine agonists (3H-dopamine and 3H-ADTN) and also of dopamine antagonists (3H-spiroperidol and 3H-domperidone) to neostriatal membrane preparations. Against dopamine agonists, ascorbic acid caused a dose-dependent inhibition of binding with about 90% effect at 6 mM ascorbic acid. Against dopamine antagonists there was U-shaped dose response curve for ascorbic acid. That is, 6 mM ascorbic acid caused no significant inhibition, while 0.006 mM caused a slight inhibition, and intermediate concentrations caused extensive inhibition. Almost identical inhibitory effects were obtained with sodium ascorbate. In other experiments, 500 mg/kg of ascorbic acid given to mice 1 hour prior to the dopamine releasing agent d-amphetamine, was able to greatly attenuate the increase in locomotor activity usually seen after amphetamine. These latter data may have important implications for a possible role for ascorbic acid in dopaminergic neurotransmission.