Neuroscientists have used human molecules to create mutant worms that don’t get drunk on alcohol.
“This is the first example of altering a human alcohol target to prevent intoxication in an animal,” says Jon Pierce-Shimomura, assistant professor at University of Texas at Austin.
An alcohol target is any neuronal molecule that binds alcohol, of which there are many.
One important aspect of this modified alcohol target, a neuronal channel called the BK channel, is that the mutation only affects its response to alcohol.
The BK channel typically regulates many important functions, including activity of neurons, blood vessels, the respiratory tract, and bladder. The alcohol-insensitive mutation does not disrupt these functions at all.
“We got pretty lucky and found a way to make the channel insensitive to alcohol without affecting its normal function,” says Pierce-Shimomura, who is corresponding author of the study published in the Journal of Neuroscience.
The research has potential applications for treating people addicted to alcohol, he says. “Our findings provide exciting evidence that future pharmaceuticals might aim at this portion of the alcohol target to prevent problems in alcohol abuse disorders. However, it remains to be seen which aspects of these disorders would benefit.”
Unlike drugs such as cocaine, which has a specific target in the nervous system, the effects of alcohol on the body are complex and have many targets across the brain. The various other aspects of alcohol addiction, such as tolerance, craving, and the symptoms of withdrawal, may be influenced by different alcohol targets.
The worms used in the study, Caenorhabditis elegans, model intoxication well. Alcohol causes the worms to slow their crawling and exhibit less wriggling from side to side. The intoxicated worms also stop laying eggs, which build up in their bodies and can be easily counted.
‘JAMES BOND’ DRUG
Unfortunately, C. elegans are not as ideal for studying the other areas of alcohol addiction, but mice make an excellent model.
The modified human BK channel used in the study, which is based on a mutation discovered by lead author and graduate student Scott Davis, could be inserted into mice. These modified mice would allow scientists to investigate whether this particular alcohol target also affects tolerance, craving, and other symptoms relevant to humans.
Pierce-Shimomura speculated that their research could even be used to develop a “James Bond” drug someday that would enable a spy to drink his opponent under the table without getting drunk himself. Such a drug could potentially be used to treat alcoholics because it would counteract the intoxicating and potentially addicting effects of the alcohol.
Research associate Luisa Scott and undergraduate student Kevin Hu were also coauthors of the study.
The ABMRF/The Foundation for Alcohol Research, the National Institute on Alcohol Abuse and Alcoholism, and the Waggoner Center for Alcohol and Addiction Research at the University of Texas at Austin provided funding for the study.
《Conserved Single Residue in the BK Potassium Channel Required for Activation by Alcohol and Intoxication in C. elegans》, Published on Journal 《The Journal of Neuroscience》in July 16, 2014.