Bile acids helps to digest fats may help treat cocaine 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 gallbladder into the upper part of the small intestine, where they emulsify fats for absorption, before being recycled further down the small intestine.
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 a reward.
The gut-to-brain axis regulates diverse behavioural phenotypes.
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.
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