Early work revealed that chronic ethanol exposure decreased glutamine synthetase while increasing glutamate and GAD in the cortex of rats.169 A more recent preclinical study found decreased GAD-67 expression levels, in the BLA, 2 months after 3 weeks of ethanol-diet initiated in adulthood, but not adolescence.170 Another study reported that chronic ethanol consumption decreased glutamine synthetase in the striatum (dorsal vs. ventral was not delineated) but not cortex of rats.171 A contemporary study also reported reduced glutamine synthetase in the brain, although the area of the brain was not identified, after chronic ethanol consumption, which started at the beginning of adolescence.172 A postmortem study indicated that glutamine synthetase was downregulated in the hippocampus of alcoholics without hepatic pathology.173 These consistent reductions in glutamine synthetase following ethanol exposure or consumption suggest the presence of astro-cytic pathology and, by extension, increased neurotoxicity. Regarding glutamate dehydrogenase, which metabolizes glutamate; adolescent binge-like drinking by rats resulted in a 40% decrease in hippocampal glutamate dehydrogenase 1, which was not seen in rats that received the same protocol during adulthood.174 Given this finding, it is noteworthy
