Digestive acids may help treat cocaine abuse

Bile acids - that help us digest fat - can help treat cocaine addiction by influencing the brain's reward system, according to a study that paves the way for new therapies against substance abuse.

Researchers from Vanderbilt University in the US first showed that surgery produced an elevation of bile acids in the brain, resulting in a reduction in dopamine release in response to cocaine.

Bile acids are normally released from the gall bladder into the upper part of the small intestine, where they emulsify fats for absorption, before being recycled further down the small intestine.

In bile diversion surgery, 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.

Mice treated with this surgery have less appetite for high-fat foods, which suggests that bile acids affect brain reward pathways.

They also showed less preference for the cocaine-associated chamber, indicating that cocaine was probably less rewarding.

The researchers next administered a drug, called OCA, that mimics the effect of bile at its receptor in the brain, called TGR5.

The study, published in the journal PLOS Biology, found that OCA mimicked the cocaine-related results of surgery in untreated mice, strengthening the case that the effects of surgery were due to elevated levels of bile acids.

Knocking out TGR5 from the brain's nucleus accumbens, a central reward region, prevented bile acids from reducing cocaine's effects, confirming that signalling through this receptor was responsible for the cocaine-related results of bile acid elevation.

"These findings redefine the physiological significance of bile acid signalling and highlight the importance of determining whether bile acid analogues represent a viable pharmacological treatment for cocaine abuse," said Aurelio Galli of the University of Alabama at Birmingham in the US.

OCA, the compound that activated the bile acid receptor in this study, is approved for the treatment of primary biliary cirrhosis (Intercept Pharmaceuticals) offering fast translational opportunities for pharmacotherapies.

This study also contributes to a greater understanding of how gut-based signalling influences higher order central functions such as reward.

The gut-to-brain axis regulates diverse behavioral phenotypes.

The researchers showed that a new gut-based bariatric surgical approach chronically elevates systemic bile acids and reduces cocaine reward.

These findings redefine the physiological significance of bile acid signalling and highlight the importance of determining whether bile acid analogues represent a viable pharmacological treatment for cocaine abuse.