UCLA Study, Alcohol/Brain/GABA

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US scientists find how alcohol causes brain intoxication
A gene mutation, which impairs brain's ability of motor coordination, may be the cause of alcoholic intoxication, US researchers reported Sunday.
Alcohol interferes with how brain cells communicate with one another, coordination, grogginess, impaired memory and loss of inhibitions associated with drunkenness. Yet scientists have been unable to pinpoint how alcohol causes this disruption in the brain.
But now, scientists at University of California, Los Angeles (UCLA), have deciphered how a naturally occurring gene mutation in rats' brains lowers the animals' tolerance to alcohol, leading to rapid and acute intoxication after the equivalent of one drink.
The study, published Sunday in the online version of Nature Neuroscience, was the first to identify how the gene variation alters GABA receptors (GABARs), namely specific sites targeted by chemicals from the brain cells, making them more responsive to very low levels of alcohol.
Alcohol enhances the GABA receptors' influence on brain cells, slowing the cells' activity and ability to communicate, said the research group led by Richard Olsen, professor at the UCLA Brain Research Institute.
"We find that alcohol impairs motor coordination by enhancing tonic inhibition mediated by a specific subtype of extrasynaptic GABA receptor expressed exclusively in cerebellar granule cells," the researchers wrote in their paper.
In recombinant studies, scientists also characterized a naturally occurring single-nucleotide polymorphism that causes a single amino acid change that can selectively increase alcohol sensitivity of GABARs.
"Behavioral and electrophysiological comparisons of genetically modified rats strongly have suggested that alcohol impairs motor coordination by enhancing granule cell tonic inhibition," they said.
The fact that the gene mutation arises naturally suggests that tolerance levels to alcohol may be genetically wired in people, too, they added.
If so, the findings could eventually help identify children and adults at higher risk of developing alcohol dependency, so these individuals can make an informed decision about whether to drink.
The study results may also speed the development of new drugs that target alcohol-sensitive GABA receptors, leading to better treatments for alcohol poisoning and addiction, the researchers said.