Studies On The Relationship And Mechanism Of Etanol-induced Release Of Ascorbic Acid And Decrease In Nitrite Levels In Striatum Of Freely Moving Mice

Acute administration of ethanol produces complex effects on the central neuronal system (CNS). For example, acute administration of ethanol induces release of ascorbic acid (AA) and decreases the levels of nitrites in the striatum of freely moving rats. Accumulating lines of evidence have demonstrated the complex relationships between ethanol, AA and nitric oxide (NO). In order to further evaluate the relationship and mechanism of ethanol-induced release of AA and decrease in the levels of nitrites in the striatum of freely moving mice, four aspects of issues were dealt with in the present thesis: 1) the role of NO in ethanol-induced release of AA in the striatum; 2) effects of the administration of exogenous AA on ethanol-induced decrease in the levels of nitrites in the striatum; 3) whether some antioxidants extracted from grape seeds could modulate ethanol-induced decrease in the levels of nitrites in the striatum; 4) the roles of glutamate receptors in ethanol-induced release of AA and decrease in the levels of nitrites in the striatum. Microdialysis coupled with HPLC-ECD was used for detection of AAand wall-reader for detection of nitrites.Results showed that L-arginine, the substrate of nitric oxide synthase (NOS), administrated intraperitoneally at the doses of 70 or 140 mg/kg or striatally at the concentrations of 1 or 10 mg/ml, had no effects on basal or ethanol (2, 4 g/kg)-induced release of AA in striatum. L-NAME, the inhibitor of NOS, administrated at the concentrations of 10-4 and 10-3 mg/ml striatally, inhibited the basal AA release and significantly antagonized ethanolnnduced AA release in the striatum. However, when administrated intraperitoneally at the doses of 70 or 140 mg/kg, L-NAME had noeffects on basal or ethanol-induced AA release in striatum. SNP, the NO donor, administrated at the concentrations of 10-4, 10-3 mg/ml striatally, decreased the basal AA levels, but had no effects on ethanol-induced AA release in striatum. The results indicate that NO may not be directly involved in the mechanism of ethanol-induced release of AA in the striatum of freely moving mice.Exogenous subcutaneous administration of AA, at the doses of 35 and 70 mg/kg, significantly increased the extracellular AA levels but had no effects on basal extracellular nitrite levels. Co-administration with ethanol, exogenous AA significantly antagonized ethanol-induced decrease in nitrite levels. The results suggest that intracellular AA levels are important in maintaining the activity of neuronal nitric oxide synthase (nNOS).Results showed that catechin, procyanidins, and resveratrol, administered at the doses of 50 or 100 mg/kg intraperitoneally, had no effects on basal AA release or nitrite levels, but significantly potentiated ethanol-induced AA release. Catechin significantly antagonized ethanol-induced decrease in nitrite levels, and procyanidins or resveratrol only showed slight effects on ethanol-induced decrease of nitrite levels. The results demonstrate for the first time that some of extracts from grape seeds could regulate the inhibitory effects of ethanol on NO production.Exogenous intracerebroventricular administration of glutamate, at the concentrations of 1 and 10 nM, increased the basal AA and nitrite levels in the striatum. Co-administration with ethanol, glutamate significantly potentiated ethanol-induced AA release and antagonized ethanol-induced decrease in nitrite levels in striatum of freely moving mice. NMDA, AMPA, and KA, administered at the concentrations of 1 and 10 nM intracerebroventricularly, increased the basal AA and nitrite levels in the striatum in different degrees. Co-administration with ethanol, NMDA, but not AMPA or KA, significantly potentiated ethanol-induced AA release and antagonized ethanol-induced decrease in nitrite levels in the striatum, which were prevented when MK-801 (10 nM) was administered intracerebroventricularly 10 min before administration of NMDA. The results suggest that NMDA receptor isspecifically involved in the mechanisms of ethanol-induced...