Researchers from Vanderbilt University suggested that bile acids reduce the rewarding properties of cocaine use.
A new research by a team from Vanderbilt University (VU) and University of Alabama at Birmingham (UAB), published in the open-access journal PLOS Biology on July 26, 2018, reported that bile acids, which primarily aid fat digestion are also found to reduce the rewarding properties of cocaine use. The research conducted by India Reddy, Nicholas Smith, and Robb Flynn of VU and Aurelio Galli of AUB point to potentially new strategies for treatment of cocaine abuse. Bile acids are steroid acids released from the gall bladder into the upper part of the small intestine. These acids emulsify fats for absorption and are recycled further down the small intestine. Bile is released at the end of the small intestine, in bile diversion surgery—an experimental treatment for weight loss that increases the amount of bile acids entering the general circulation. Mouse models treated with this surgery show significant decrease in appetite for high-fat foods. This tendency reveals that bile acids are responsible for brain’s reward system.
The researchers observed the surgery produced large amount of bile acids in the brain that significantly reduced the amount of dopamine released in response to cocaine. Similar results were evident in the mouse models that showed less preference for the cocaine-associated chamber. Such behavior in the animals suggested that cocaine was probably less rewarding due to enhancement of bile acid. Administration of a drug—OCA— that mimics the effect of bile at TGR5—a bile receptor in the brain led to OCA mimicking the cocaine-related results of surgery in untreated mice. The mimicking of OCA further proved that the effects of surgery were due to elevated levels of bile acids. Eliminating TGR5 from the brain’s nucleus accumbens—a central reward region resulted in enhancing the cocaine effects. This deliberate knock out of TGRS confirmed that signaling through this receptor was responsible for the cocaine-related results of bile acid elevation.