Chronic- and relapse-alcohol drinking reduce local cerebral glucose utilization rates in alcohol-preferring P rats

The 2-[14C]-deoxyglucose (2-DG) quantitative autoradiography technique was used to determine local cerebral glucose utilization (LCGU) rates in alcohol-naive alcohol-preferring (P), alcohol non-preferring (NP) and Wistar rats, and the effects of chronic alcohol drinking and alcohol relapse drinking in discrete brain regions in adult, male P rats. The hypotheses were, in experiment l: selective breeding for high alcohol drinking behavior produces hereditary differences in LCGU rates within key limbic regions; experiment 2: neuronal alterations occur as a result of chronic alcohol drinking and persist in the absence of alcohol; experiment 3: alcohol-relapse drinking returns LCGU rates which had recovered to normal levels during alcohol deprivation, to the chronic alcohol state. [14C]2-DG (125 μCi/kg) was injected intravenously and timed arterial blood samples were collected over the following 45 min and assayed for glucose and [14C]2-DG content. Rats were then decapitated; the brains removed, frozen to −70°C, and sectioned for quantitative autoradiographic analysis. LCGU rates were determined in 55 to 59 regions and subregions. The results demonstrated that (1) LCGU rates were significantly higher in several limbic, cortical and subcortical structures in P, compared to NP and Wistar rats, (2) 6–8 weeks of daily 4-hour limited-access alcohol consumption produced significant reductions in LCGU rates in most CNS regions of the P rat, some of which persisted in the absence of ethanol, and (3) compared to LCGU values that recovered toward normal levels after a 2-week alcohol deprivation period, relapse drinking decreased LCGU values in limbic, cerebral cortical and subcortical structures. The data suggest that (1) selective breeding for high alcohol drinking produces intrinsically higher functional neuronal activity in many CNS regions of P compared to NP or Wistar rats, (2) chronic alcohol drinking generally reduces this higher activity, (3) the persistence of the reduced functional activity in some CNS regions and the recovery of activity in other regions following deprivation suggests that neuronal imbalances exist which represent neither the “alcohol” nor the “normal” state, and (4) relapse drinking may be initiated to restore these imbalances to the “alcohol” state