Differential brain metabolism following single vs. repeated ethanol exposures in adolescent rat: A [18F]fluorodeoxyglucose-PET study

Objectives Alcohol drinking among teenagers and young adults is a major health concern. Earlier we have shown that ethanol disrupts the acquisition of spatial memory in adolescent rats. FDG-uptake PET studies have been used to identify metabolic signatures in brains of human alcoholics. Here we tested the hypothesis that ethanol exposure in adolescent rat produces metabolic changes in specific brain regions.

Methods Using 18F-FDG PET, we measured glucose metabolism in the brain of adolescent Sprague-Dawley rats under baseline condition, and following single ethanol (2g/kg) exposure, repeated (2g/kg) ethanol administrations, and long-term withdrawal. Rats were anaesthetized and their brains scanned. Scan 1: baseline, Scan 2: acute ethanol treatment, Scan 3: 1-day withdrawal after daily ethanol treatment for short duration (5 days), Scan 4: 1-day withdrawal after daily ethanol treatment for long duration (20 days), Scan 5: one month after last ethanol administration.

Results Significant increases in 18F-FDG were seen in several brain regions following a single ethanol exposure. Following repeated ethanol treatments, whole brain FDG uptake showed significant decrease, with greater attenuations after long exposure (20 days) than shorter exposure (5 days). There was a significant rebound in FDG uptake following cessation of ethanol administration.

Conclusions Ethanol exposure produced region-specific changes in brain metabolism. Acute ethanol increased brain metabolism, whereas 1-day withdrawal following repeated ethanol treatment significantly attenuated metabolic functions in cortical and subcortical structures. These changes were reversed after cessation of ethanol exposure. Our results suggest that ethanol in adolescent rat differentially affects brain functions following acute vs. repeated administrations.

Research Support NIH AA-017359 to R