Drinking without getting drunk?

December 7, 2015

They call the project “The Mutant Mouse that Cannot Get Drunk” – at least that’s how it’s described by the successful Hornraiser fundraising campaign that raised over $13K for UT Austin’s Waggoner Center for Alcohol & Addiction Research. The funds will go to creating and studying the mouse in the lab in the quest to better understand and treat alcoholism.

Heading the project is neuroscience professor Jon Pierce-Shimomura, researcher in genetic disorders at the University of Texas at Austin. Among the ailments he’s most interested in is Alcoholism. As he told the Austin American-Statesman, the genetic factors behind this disease have yet to be sufficiently studied.

“Right now, believe it or not, scientists still don’t know the answer to the fundamental question of how we get drunk,” he said. “What we’re excited about is the potential for treating people at the point … where they’re really vulnerable because they’re dealing with these often-intense withdrawal symptoms.”

So, just how does Pierce-Shimomura plan on better understanding the mechanisms behind inebriation and eventual alcohol addiction? By creating a genetically-modified mouse that can’t get drunk.

 A truly mighty mouse

Pierce-Shimomura recently joined forces with several UT graduate students and researchers, plus experts from the Oregon Health & Science University, to create the aptly-titled Supermouse funded through UT’s HornRaiser program, which helps generate research money for a slew of scientific projects across the entire Austin-based campus. It took the Supermouse campaign  just over 15 days (of a 30-day charity drive running through Dec. 5, 2015) to surpass its goal of $12,000.

To create this specimen of mousedom, the research collective is modifying a lab rat’s BK (“Big Potassium”) channels after studying the way alcohol targets and binds with these channels. When activated, the BK channel is thought to impact neurons and muscles in such a way as to create the familiar sluggish reaction to alcohol.

BK channels are responsible for all living creatures’ reactions to alcohol.

By studying the Supermouse, researchers will be one step closer (after successful research with worms) to understanding and preventing alcohol intoxication and withdrawal in humans. The team specifically said that looking at the withdrawal phase of alcohol consumption is a good place to start. Speaking with The Daily Texan, UT research associate Luisa Scott said,

“Withdrawal is the perfect point of intervention for breaking the cycle of alcohol abuse,” she said. “Research supports the idea that minimizing the physiological and psychological discomfort of withdrawal helps reduce chances of relapse. Hopefully, Supermouse research will result in treatments that provide support and guidance to patients experiencing withdrawal.”

Alcohol is something of a unique substance, according to Psychology Today. While drugs like heroin and cocaine target specific parts of the brain, alcohol has a much wider impact.  For instance, withdrawal can present in several different systems of the brain and body, causing fever, hand tremors, seizures and even hallucinations.

It all started with a drunken worm

While blocking the BK channel could interfere with higher functions, like regulating blood pressure and balance, the team learned that singling out and mutating a portion of the channel could avoid these effects. Back in July 2014, Pierce-Shimomura and another research team released a study in which they identified BK channel mutations in worms of the species Caenorhabditis elegans that essentially produced  a perpetually sober worm, publishing the results in The Journal of Neuroscience.

Worms almost perfectly model intoxication.

“We got pretty lucky and found a way to make the channel insensitive to alcohol without affecting its normal function,” Pierce-Shimomura said about the research in the UT press release.

The research team began with worms because of how well they model alcohol intoxication. Not only do worms begin to wiggle lopsidedly once inebriated, they also stop laying eggs and instead store them, which scientists can use as a measurable sign of alcohol consumption, according to the accompanying press release.

However, worms aren’t necessarily the greatest model for understanding human physiology; hence the switch to mice. As researchers told The Daily Texan, worms are far too simple biologically. For instance, worms didn’t offer researchers enough insight into cravings. They lack the complexity and other variables needed to better understand alcohol consumption in mammals.

The plan for Supermouse is to reproduce this specific mutation in the mouse – leaving, as with the worm, other functions of the BK channel in tact – so as to observe the effect of alcohol on its system. What impact the mutation has on other aspects of alcoholism, such as cravings, remains to be seen. And further down the line, filtered through human experience, how will the approach “work” when it meets human behavior?

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