Metabolic mapping of the effects of oral alcohol self-administration in rats

The functional effects of the voluntary consumption of ethanol in rats were investigated using the quantitative autoradiographic 2-[14C]deoxyglucose method for measurement of rates of local cerebral glucose utilization. A modified sucrose-substitution procedure was used to train three groups of Wistar rats to self-administer water, a 5% sucrose solution, or a 10% ethanol/5% sucrose solution in daily sessions. Once stable rates of consumption were established, the 2-[14C]deoxyglucose method was applied immediately after completion of the final test session. Rats received a dose of ethanol equivalent to 0.5 g/kg (n = 6) on the day of the procedure or a comparable volume of sucrose solution (n = 6) or water (n = 5). Rates of local cerebral glucose utilization in rats that ingested water did not differ from those that rats consumed a 5% sucrose solution. In contrast, voluntary ethanol consumption produced a highly discrete pattern of changes in rates of glucose utilization. Ethanol ingestion increased cerebral metabolism, as compared with rates of metabolism in rats that consumed either water or sucrose in the rostral pole and shell of the nucleus accumbens, medial prefrontal cortex, lateral septum, basolateral and central nuclei of the amygdala, substantia nigra, and the ventral tegmental area. This pattern of alterations in functional activity is distinctly different from that observed when equivalent doses of ethanol are administered acutely, emphasizing the importance of self-administration in determining the changes in glucose utilization. Furthermore, within the nucleus accumbens, glucose utilization was selectively augmented in the rostral pole and shell subterritories, whereas cerebral metabolism in the core was unaffected. Finally, these data demonstrate that it is the simultaneous activation of an interconnected network of limbic brain regions that serves as the substrate of the effects of voluntarily ingested ethanol.