Ascorbic acid and atypical antipsychotic drugs: modulation of amineptine-induced behavior in mice

To provide a detailed characterization of individual kinds of behavior produced by ascorbic acid in combination with typical (haloperidol) or atypical (clozapine, sulpiride and remoxipride) antipsychotic drugs, the 'open-field' test was selected. Amineptine, an indirect dopamine agonist, was used as an explicit model of dopaminergic activity. Results showed that amineptine (5-10-20 mg/kg i.p.), dose-dependently, increased ambulation and rearing. Ascorbic acid (62.5-125-250 mg/kg i.p.) markedly inhibited the behavior of mice as well as the amineptine-induced hyperactivity. A combination of each typical or atypical antipsychotic drug (except clozapine 2.5 mg/kg i.p.) with amineptine (20 mg/kg i.p.) induced a significant increase in ambulation and rearing over that seen with the antipsychotic drugs alone. The combination of antipsychotic drugs with ascorbic acid 250 mg/kg i.p. led to a decrease in open-field parameters when compared with controls. In conclusion, these data provide further in vivo support for the effect of ascorbic acid on dopaminergic system and demonstrate that the antidopaminergic effects of both typical and atypical antipsychotic drugs may be enhanced with concurrent administration of ascorbic acid.