Cocaine Addiction Uses Same Brain Paths as Salt Cravings

Drugs such as heroin and cocaine may owe some of their addictive powers to an ancient instinct—our appetite for salt.

In a new study of mouse brains, scientists show that the patterns of gene regulation stimulated by salt cravings are the same gene patterns regulated by drug addiction.

Salt appetite is a craving millions of years in the making, with likely roots in the salty seas where life on Earth began. (Related: "Is Salt Nature's Antidepressant?")

"Land dwellers face a problem in that sodium is a trace element, so they have to have a strategy to ingest sodium, and salt craving or sodium appetite is evolution's answer to that," said study co-author Wolfgang Liedtke, an assistant professor of medicine and neurobiology at Duke University.

Salt appetite can be so strong that animals short on sodium will put life and limb at risk to satisfy the hunger. Mountain goats, for instance, are known to cling to sheer cliffs to access a salt lick, even when a misstep means certain death. (Related pictures: "Goats Scale Dam in Italy.")

The new finding suggests that drug addictions may be so hard to overcome in part because cocaine and opiates—both derived from plants—exploit the brain mechanisms critical for salt appetite.

"Cocaine can usurp the ancient [neural] systems that have made animals better survivors," Liedtke said.

The research offers some of the first evidence for addiction processes previously theorized by other experts, added study co-author Derek Denton of the University of Melbourne and the Florey Neuroscience Institute.

Salt Cravings Lead to Rapid Brain Change

Denton, Liedtke, and colleagues used several techniques to figure out which genes in mammal brains were activated by salt cravings, such as withholding salt from test mice or increasing their salt needs by giving them the stress hormone ACTH.

The team noticed that, almost as soon as the salt-depleted mice started drinking salt water, the patterns of gene regulation triggered by the need began to reverse.

The rapid response is a surprise, because it means brain changes in the mice occurred before significant amounts of salt had moved from the stomach to the bloodstream.

"It was stunning and perplexing to see that just ten minutes of drinking salty water led to a complete change of the whole sophisticated and elaborate genetic program," Duke's Liedtke said.

(Related: "Cocaine, Spices, Hormones Found in Drinking Water.")

Addiction Drivers Still Unknown

It's possible that the research may lead to new treatments for drug addiction that don't rely on "cold turkey" abstinence, which is less likely to be successful against such strong, instinctual cravings.

Overall, though, Liedtke cautions that the new study doesn't fully explain the neural drivers of drug addiction.

"Sodium appetite is a healthy instinct. Heroin addiction is a disease that can kill a human," he said. "To go from a healthy instinct to a malady, other things must be happening in the brain."

The salt-appetite research was published online in the early edition of the Proceedings of the National Academy of Sciences.