Binge Drinking +/– Chronic Nicotine Administration Alters Extracellular Glutamate and Arginine Levels in the Nucleus Accumbensn of Adult Male and Female Wistar Rats

摘要

Aims: The effect of ‘binge drinking’ coupled or not with chronic nicotine administration on nucleus accumbens (NAc) glutamate, arginine, taurine and hydroxyl radical levels has been investigated in these present studies. Methods and Results: Ethanol, 2 or 3 g/kg, has been administered to male or female adult rats in a ‘binge-type’ regime for 3 weeks, +/– nicotine, and changes in glutamate, arginine and taurine content in the NAc, assayed by microdialysis after a further dose of ethanol. The basal concentration of NAc glutamate increased 8-fold in the female adult rats but did not change significantly after further doses of ethanol. In contrast, the male adult rats showed no changes in basal glutamate content but exhibited a dose-dependent increase in NAc glutamate after further doses of ethanol. NAc arginine basal levels decreased significantly in both male and female adult rats after further doses of ethanol. Co-administration of nicotine modified the toxicity of ethanol as exemplified by diminishment of both the basal NAc glutamate release as well as modifying the release of this excitatory amino acid after further ethanol doses, particularly in female rats. In addition, the marked changes in arginine release after further ethanol doses were less evident. There was no evidence for increased hydroxyl radical production in the NAc after ‘binge drinking’ +/– nicotine. Conclusion: There appeared to be a greater vulnerability to ethanol toxicity in female adult rats after ‘binge drinking’. It remains unclear whether the increased release of glutamate during the microdialysis evokes activation of inducible nitric oxide synthase (iNOS), which would utilize arginine in the formation of nitric oxide.