Potentiation of ethanol-induced loss of the righting reflex by ascorbic acid in mice: interaction with dopamine antagonists.

The present investigation was carried out to determine the effect of ascorbic acid on ethanol-induced loss of the righting reflex (LORR) and the interactions between ascorbic acid and dopamine receptor antagonists in affecting this action of ethanol in mice. To test the effect of each drug on ethanol-induced LORR, ascorbic acid (31.25, 62.5, 125, 250, 500, 1000 mg/kg intraperitoneally [IP]) and dopamine receptor antagonists (haloperidol 0.5, 1.0 mg/kg; L-sulpiride 20, 40, 80 mg/kg; clozapine 0.625, 1.25, 2.5 mg/kg; SCH 23390 0.5, 1.0, 2.0 mg/kg subcutaneously [SC]) were administered, respectively, 30 min before ethanol (4.0 g/kg IP) administration. Ascorbic acid, at the dose of 1000 mg/kg, significantly potentiated ethanol-induced LORR in mice. Dopamine D(2) antagonists haloperidol (0.5, 1.0 mg/kg SC), and L-sulpiride (80 mg/kg SC) also significantly prolonged the duration of LORR induced by ethanol. Clozapine and SCH 23390, at the doses used, did not affect ethanol-induced LORR. In the interaction study, the synergistic effect of ascorbic acid (1000 mg/kg IP) on ethanol-induced LORR was significantly enhanced by dopamine D(2) antagonists haloperidol, L-sulpiride, and clozapine, and the highest dose of dopamine D(1) antagonist SCH 23390. These results suggest that ascorbic acid may potentiate ethanol-induced LORR partially via a mechanism mainly linked to blockade of dopamine D(2) receptors.