II - FUNCTIONAL CONSEQUENCES OF INTRAGASTRICALLY ADMINISTERED ETHANOLIN RATS AS MEASURED BY THE 2-[C-14]DEOXYGLUCOSE METHOD - THE CONTRIBUTION OF DOPAMINE

As outlined in the companion paper, many of the changes in functional activity produced by acute intragastric ethanol administration as dete rmined by the quantitative autoradiographic 2-[C-14]deoxyglucose metho d occur in structures of the mesocorticolimbic and nigrostriatal dopam ine circuits. In this study, a dopaminergic antagonist, flupenthixol, was used to determine the contribution of dopamine to the ethanol-indu ced increases in functional activity. To assess the ability of flupent hixol to block dopaminergic-induced increases in glucose utilization, it was first examined in conjunction with the indirect dopaminergic ag onist methylphenidate. Pretreatment with flupenthixol significantly re duced methylphenidate-induced increases in glucose utilization in stru ctures of the mesocorticolimbic and nigrostriatal dopamine circuits. T hese findings indicate that this is an effective strategy for the dete rmination of the neurochemical contributions to the changes in CNS fun ctional activity. Flupenthixol pretreatment blocked many of the ethano l-induced increases in glucose utilization at the 0.25 g/kg dose, part icularly in mesocorticolimbic and nigrostriatal structures, At the 1.0 and 2.0 g/kg ethanol doses, however, pretreatment with flupenthixol d id not reverse the increases in glucose utilization in several brain r egions, suggesting that dopaminergic activity is not responsible for t he observed increases in glucose utilization and further, that these i ncreases involve other neurotransmitter systems. In some regions, howe ver, flupenthixol pretreatment resulted in augmented levels of glucose utilization above those rates produced by the administration of highe r doses of ethanol alone. These findings suggest that the contribution of dopamine to the increases in functional activity are more complex at higher doses of ethanol.