Ethanol: Protracted Changes in Brain Glucose Metabolism

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DESCRIPTION (provided by applicant): In the alcoholic, even after the cessation of drinking, there may be residual effects that last for months and possibly years. The abstinent alcoholic, for a variety of reasons, will have a craving for alcohol long after the last drink. Although there is evidence that chronic ethanol administration in rodents can cause neuroanatomical damage with concomitant cognitive deficits, there has been only a slight suggestion that there may be post-withdrawal changes in functional local cerebral metabolic glucose utilization. Although craving is generally believed to be cue manifested the only animal experimental models of cue induced intracerebral changes have been confined to the study of the measurement of neurotransmitter changes 24 hours after the last of a number of repeated ethanol doses. The specific aims of the research is to test the hypothesis that there are protracted changes in basal cerebral metabolism resulting from oral self- administration of alcohol and that these effects are enhanced by the presence of alcohol cues. The proposed experiments will use the quantitative 2-deoxy-D-[I- 14C]glucose (2-DG) autoradiographic method to determine the local cerebral metabolic rates of glucose a number of weeks after the cessation of daily oral self-administration of ethanol in the Wistar rat. These effects will be studied in the presence and absence of cues associated with the ingestion of the ethanol. The 2-DG analysis will focus on those interconnected regions of the limbic system that have been shown to be altered by chronic oral ethanol self- administration. Positive findings will allow for future research directed toward the understanding of the mechanisms involved in these protracted effects and the developments of possible pharmacological interventions that will interfere with these actions.