By Kendall Morgan, GenomeLIFE
In our fast-food culture, it’s hard to imagine what it must feel like to really need salt. But our bodies, and every one of our cells, do need salt, just as all animals do. Goats will famously risk their lives scaling impressive vertical climbs just to reach salt-encrusted stones high above. When an animal craves salt, nothing else will do.
“This instinct evolved over hundreds of millions of years,” said Wolfgang Liedtke, an associate professor in the Duke University departments of medicine and neurobiology. “It is essential to survival, an inborn craving. Nature could take no risk.”
It turns out that this essential survival instinct helps to explain modern problems other than our love for potato chips. In 2011, Liedtke and his colleagues reported evidence in The Proceedings of the National Academy of Sciences that these ancient pathways are the very ones underlying drug addiction. Drugs, it appears, have an ability to hijack the same neural pathways and connections that our lives have depended on for so long to secure one of our most basic needs. The human urge to satisfy drug cravings runs very deep indeed.
Now, with the help of support from the IGSP’s interdisciplinary award program last year, Liedtke and his colleagues want to know if they might find some parallels and additional insight by studying thirst for water, too.
Rewards On The Brain
In the beginning, Liedtke wasn’t after the roots of addiction at all. His studies in mice were designed to show how genes are expressed in a part of the brain called the hypothalamus to control the equilibrium of salt and water, and to identify new genes with critical functions. When the data came back from the IGSP’s Microarray Core Facility, he noticed something right away: The genes at the top of the list were already well known for their roles in addictive disorders from studies in animal and human tissues.
Careful use of statistical analyses developed in part by Liedtke’s IGSP collaborator and computational biologist Sayan Mukherjee, resoundingly confirmed that initial observation. Those reward and addiction-related genes turned up not only in mice that were deprived of salt, but also in those fooled into craving salt with a hormone. The findings confirmed that the genetic programs they had uncovered really reflected salt craving and were not brought on simply by stress.
The researchers were further surprised and gratified to find that blocking those addiction-related pathways in a portion of the hypothalamus could powerfully interfere with sodium appetite. “Our findings have profound and far-reaching medical implications and could lead to a new understanding of addictions and related problems, such as when obesity-generating foods are overloaded with sodium,” Liedtke said when the paper, which some have since called a “game changer,” first came out.
Their ongoing studies in thirsty mice aim to look for similarities and differences between the instinctive needs for salt and water and the relief that comes when those cravings are satisfied. It’s already clear that thirst, like salt craving, involves dopamine receptors and dopamine, which is the currency for pleasure in the brain.
Rethinking Society’s View Of ‘Moral Failures’
When Owen Flanagan, Duke professor of philosophy and a member of the research team, first caught wind of the discovery that addictions work essentially as artificial instincts, he was immediately intrigued. “This speaks to questions about to what extent addicts are morally responsible for their actions–to what extent their brains have been hijacked,” he says.
Those are issues that Flanagan has long grappled with personally and professionally, inspired initially by family members over the course of generations who had spun out of control of their lives and for those who acted out of sympathy for them. With the biology in view, he says it becomes harder to think of addictions as simple moral failures in the way society so often does.
“Understanding what happens at the level of gene regulation allows us to see the causal picture more clearly,” Flanagan said. “It allows us to imagine interventions of various kinds.”
Addiction is a challenge for Liedtke as well, as he struggles to understand and manage patients suffering from chronic pain at the Duke Pain Clinic. “Addiction interferes with my attempts to treat pain; it is a daily reality for me,” Liedtke said. “The question is how do we as a society come to see addiction and addictive behaviors. Where do they come from? What’s behind it?”
He isn’t hopeful that one could deal with addictions effectively by blocking these primal urges outright; they are essential survival instincts after all.
“But,” he says, “I certainly would not suggest a strategy that leaves this insight unaccounted for.”
Maybe, just maybe, the efforts of Liedtke and his team can lead to new and more constructive approaches to the addiction problem, even if the change that happens is primarily in our minds.