Bile acids – crucial for the digestion and absorption of fats and lipid soluble vitamins in the small intestine – may reduce the desire for cocaine
Researchers at the Vanderbilt University Medical Center and the University of Alabama in Birmingham suggest that Targeted bile acid signaling in the brain could be a new way to treat cocaine abuse.
Vanderbilt investigator Charles (Robb) Flynn and Naji Abumrad, John L. Sawyer's Professor of Surgical Sciences, have long been studying the metabolic changes associated with bariatric surgery for weight loss.
"Surgical patients are experiencing dramatic changes in glucose regulation and in taste preferences and cravings while they are still in the recovery room," said Flynn.
"These surgeries do a bit more than we understand, and we were wondering if elevated bile acids, a hallmark of bariatric surgery, affected the reward centers of the brain to reduce the enjoyment of eating high-fat foods," he said.
When the operation affected the reward centers of the brain, he added, "How could it influence the rewarding properties of drugs from abuse?"
The most common bariatric surgery ̵
To investigate the effects of bariatric surgery and elevated bile acids, Flynns group developed a simpler surgical procedure in mice called bile drainage, in which the gallbladder is surgically connected to the end of the small intestine. DB = EPODOC & … PN = EP0288656 Gull drainage in an overweight mouse has all the benefits of bariatric surgery: weight loss, reduced food intake and improved oral glucose tolerance, said Flynn.
With colleagues Aurelio Galli, the researchers found that bile secretion in normal-weight mice reduced the cocaine-induced increase in brain dopamine release and decreased cocaine-associated behavior.
The researchers tested the effects of a synthetic bile acid called obeticholic acid (OCA), which is clinically approved for the treatment of chronic liver disease primary gallbladder cholangitis. In non-surgical mice, OCA administration mimicked the effects of bile secretion in reducing cocaine-associated behaviors.
The researchers also demonstrated that the bile acid TGR5 receptor mediates the effects of increased bile acids and OCA in the nucleus accumbens, a brain that plays a key role in the reward circuit.
The study is the first to demonstrate a role for the bile acid central nervous system in changing reward-related behaviors and opens the possibility to treat drug abuse in new ways  "Will bile acids cure cocaine addiction in humans? We do not know, but our research suggests that bariatric surgery or the consumption of bile acids might have a positive impact, "said Flynn.
The study appears in the journal PLOS Biology
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