Researchers in Massachusetts say they’ve found a neurological needle in the haystack – neurons that could mean the difference between stopping after a drink or two or going overboard and binge drinking.
The NIH-funded research involved mice, but with follow-up, the discovery could have major implications for treating humans with alcohol addiction.
Dr. Gilles Martin tells WAMC he’s long been interested in exactly what the brain does in response to alcohol consumption.
An associate professor of neurobiology at the UMass Chan Medical School in Worcester, he says compared to other things we ingest or inject to feel pleasure, booze doesn’t activate the brain’s reward center the way a good meal or certain drugs might.
In fact, as a paper that caught his eye 30 years ago found, alcohol doesn’t seem to activate all that many cells in the brain to begin with.
“This paper showed that when you give alcohol to a mouse or rat, only very few cells are actually activated,” he says. “You take for instance the nucleus accumbens … what probably everybody knows to be the reward center of the brain’ - when you do something very pleasurable, when you take a drug you should not or when you eat really something absolutely delicious, this is the part of the brain that will say, ‘Well, this is really good. I should really get more of it.’ This paper, when it came out, it showed that only very, very few cells/neurons in these brain regions were actually activated by alcohol – I was very intrigued.”
Years later, he and a team of UMass Chan staff and others recently wrapped up their own project also using mice. In the process, they discovered a series of neurons that appear to have a sizable effect on how much drinking a mouse might do before calling it quits.
For context – the human brain is home to billions upon billions of neurons. A mouse meanwhile, is more in the realm of 70 million, some estimate.
Martin, lead author of the paper published in Nature Neuroscience, says his team was able to use an array of technologies to narrow down parts of the brain activated by alcohol – only a few hundred neurons that seem to act as a proverbial brake, discouraging excessive alcohol consumption.
“What we found is that there is a region in the prefrontal cortex, called the medial orbitofrontal cortex, where there is really a few cells that are activated,” Martin says. “It’s really a back-of-the-envelope calculation, but my estimate is about 500 cells, based on the density of neurons in this brain region and the number of cells that are turned on by alcohol.”
“We found this cluster of 500 cells that we call a ‘neuronal ensemble,’ that is activated by alcohol and when they are activated by alcohol. they reduce alcohol consumption,” he continues. “If we ablate the cells or if we turn them off using a technique that is called optogenetics - we use light to turn them off - when we do that, the alcohol consumption really goes up and for weeks.”
Using the aforementioned techniques, the researchers’ setup allowed them to see what kind of excess the rodents indulge in when the switch is flipped off and a sort of pseudo-temperance when it’s on.
“… when we ‘turned off’ these neurons, the mice were really drinking much, much more,” he explains. “… our little setup, it's very simple - it's a bottle that contains 20 percent alcohol and there is a spout and the animal is really completely free to drink or not to drink - there is really absolutely no constraints - I mean, nothing. When we turn off these neurons, you can see the mice really go to the spout much more often and they really drink much more and when we do the opposite, when we excite these neurons… well, all of a sudden, the mice don't seem to really care that much about the alcohol.”
It's a discovery that, if pursued and studied further, could have major implications in the world of treating alcohol abuse – leading to improved therapeutics.
Martin tells WAMC that in terms of medications currently on the market, there aren’t too many stellar options for those dealing with alcohol addiction. A number of drugs tend to target neuroreceptors across the brain and often pack side effects so potent, those in need might be discouraged from taking them.
To be able to pinpoint parts of the brain where alcohol does its thing could lead to better, targeted treatments for one of the world’s leading causes of death.
Binge drinking in the United Sates is said to affect over 16 million people ages 12 and up, Martin explains in an article he authored for The Conversation.
“When alcohol is onboard, these neurons are activated to reduce alcohol consumption and this is where I think the paper is really getting some attention - because typically, when you take a drug of abuse - cocaine or heroin - it will have reinforcing properties, meaning that you say, ‘Oh, my God, this is really good. I'm going to take some more,’ and this is, to my knowledge, the first time that someone is showing that a drug of abuse like alcohol … [is] certainly also doing that, but is also activating this cluster of neurons that will counteract its reinforcing properties,” he says. “This is really something really, really cool.”
Martin emphasizes that while mice brains and human brains share similarities, making rodents great for neuroscience research, that doesn’t necessarily mean human brains have the same setup for dealing with binge drinking - there’s follow-up research to be done, he says.
In a write-up on the UMass Chan website, he ventures to say the number of core neurons that affect binge drinking could also be even smaller.
He hopes to see further research funded, though he adds that, among his colleagues and beyond, there’s ongoing concern over where that money might come from.
For example, Martin’s team was the recipient of an R01 grant from the National Institutes of Health, which has been implementing largescale cuts over the past few months.
Federal authorities have cited a need to scale back and cut spending considered to be wasteful – something researchers, educators and Governor Maura Healey heavily-dispute.
It’s meant significant cutbacks for universities like UMass Chan, which received $193 million from the NIH last year and now faces a $35 million shortfall, it reported in April. Layoffs, furloughs and freezes have followed in the wake of the announced cuts.
Martin says the changes at the NIH are having a ripple effect across the research community, with aftershocks to be felt for years to come, especially if more cuts are on the horizon.
“The impact would be long-term, certainly, because if this budget is voted [through], it's very likely that some labs will certainly shut down,” he says. “And even more worrisome is the fact that a new generation of scientists is going to look elsewhere, because when you go to grad school now … well, the number of labs where you're going to do your work is going to be limited and frankly, this is not exactly the environment you want to commit to for the next five to six years of your life, not knowing what will be the options at the end of your PhD.”
