NMDA receptor antagonist CPP inhibits ethanol-evoked ascorbate release in the brain of freely moving rats

The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), on the ethanol-evoked release of brain ascorbate (AA) was investigated in freely moving rats using an in vivo voltammetry technique. Ethanol (1.0 g/kg, intraperitoneal injection, i.p.) increased the release of brain AA in the nucleus accumbens and striatum. Pretreatment with CPP (1 nmol, intracerebroventricular injection, i.c.v.) not only completely reversed the ethanol-evoked AA release but also reduced the concentration of extracellular AA and kept it at low level 80 min after the ethanol administration in both brain areas. However, 80 min after the treatment with CPP per se only the level of AA in the nucleus accumbens was decreased. The results suggest that ethanol-evoked release of AA probably is a self-protective mechanism against the neurotoxicity induced by ethanol in the brain, and the NMDA receptor may play an important role in this mechanism.