Bile acids that help with fat digestion can also reduce the “rewarding” feelings of cocaine use, according to a study published recently in PLOS Biology by India Reddy, Nicholas Smith, and Robb Flynn of Vanderbilt University, Aurelio Galli of the University of Alabama at Birmingham, and their colleagues, according to Science Daily. The results show promise for potential new strategies for treatment of cocaine abuse.
This study builds on evidence that bile acids influence the brain’s reward system. Bile acids are normally released from the gall bladder into the upper part of the small intestine, where they break down fats for absorption, before being recycled further down the small intestine. In bile diversion surgery, which is an experimental treatment for weight loss, bile is released at the end of the small intestine, increasing the amount of bile acids that enter the general circulation.
The researchers first showed that the surgery produced an increase of bile acids in the brain, resulting in a reduction in dopamine release in response to cocaine. Mice receiving the surgery also showed less preference for the cocaine-associated chamber, indicating that cocaine was probably less rewarding.
The researchers then administered a drug, called OCA, that mimics the effect of bile at its receptor in the brain, called TGR5. They found that OCA mimicked cocaine-related results of surgery in untreated mice. Removing TGR5 from the brain’s nucleus accumbens, a central reward region, prevented bile acids from reducing cocaine’s effects, confirming the hypothesis.
“These findings redefine the physiological significance of bile acid signaling and highlight the importance of determining whether bile acid analogues represent a viable pharmacological treatment for cocaine abuse,” Galli said.