Bile acids from the gut could help to treat cocaine abuse

July 26, 2018

Bile acids that aid fat digestion are also found to reduce the rewarding properties of cocaine use, according to a study publishing on July 26 in the open-access journal PLOS Biology by India Reddy, Nicholas Smith, and Robb Flynn of Vanderbilt University, Aurelio Galli of the University of Alabama at Birmingham, and colleagues. The results point to potential new strategies for treatment of cocaine abuse.

The 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 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.

To test this hypothesis, the authors first showed that surgery produced an elevation 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 authors next administered a drug, called OCA, that mimics the effect of bile at its receptor in the brain, called TGR5. They 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 signaling through this receptor was responsible for the cocaine-related results of bile acid elevation.

"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. 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 signaling influences higher order central functions such as reward.

The gut-to-brain axis regulates diverse behavioral phenotypes. The authors reveal 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 signaling and highlight the importance of determining whether bile acid analogues represent a viable pharmacological treatment for cocaine abuse.
-end-
In your coverage please use this URL to provide access to the freely available article in PLOS Biology: http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2006682

Citation: Reddy IA, Smith NK, Erreger K, Ghose D, Saunders C, Foster DJ, et al. (2018) Bile diversion, a bariatric surgery, and bile acid signaling reduce central cocaine reward. PLoS Biol 16(7): e2006682. https://doi.org/10.1371/journal.pbio.2006682

Image Caption: Researchers reveal that bile acids from the gut reduce cocaine's effects in the brain, which may offer drug addiction treatment.

Image Credit: Sammisreachers on Pixabay

Funding: NIH http://www.nih.gov (grant number 007347). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NIH (grant number 038058). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NIH http://www.nih.gov (grant number 036940). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NIH http://www.nih.gov (grant number 015388). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NIH http://www.nig.gov (grant number 105847). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NIH http://www.nih.gov (grant number 035263). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

PLOS

Related Cocaine Articles from Brightsurf:

Sleep-deprived mice find cocaine more rewarding
Sleep deprivation may pave the way to cocaine addiction. Too-little sleep can increase the rewarding properties of cocaine, according to new research in mice published in eNeuro.

Nucleus accumbens recruited by cocaine, sugar are different
In a study using genetically modified mice, a University of Wyoming faculty member found that the nucleus accumbens recruited by cocaine use are largely distinct from nucleus accumbens recruited by sucrose, or table sugar.

Astrocytes build synapses after cocaine use in mice
Drugs of abuse, like cocaine, are so addictive due in part to their cellular interaction, creating strong cellular memories in the brain that promote compulsive behaviors.

Of all professions, construction workers most likely to use opioids and cocaine
Construction workers are more likely to use drugs than workers in other professions, finds a study by the Center for Drug Use and HIV/HCV Research (CDUHR) at NYU College of Global Public Health.

Chronic cocaine use modifies gene expression
Chronic cocaine use changes gene expression in the hippocampus, according to research in mice recently published in JNeurosci.

Blocking dopamine weakens effects of cocaine
Blocking dopamine receptors in different regions of the amygdala reduces drug seeking and taking behavior with varying longevity, according to research in rats published in eNeuro.

Born to run: just not on cocaine
A study finds a surprising response to cocaine in a novel strain of mutant mice -- they failed to show hyperactivity seen in normal mice when given cocaine and didn't run around.

Cocaine adulterant may cause brain damage
People who regularly take cocaine cut with the animal anti-worming agent levamisole demonstrate impaired cognitive performance and a thinned prefrontal cortex.

Setting affects pleasure of heroin and cocaine
Drug users show substance-specific differences in the rewarding effects of heroin versus cocaine depending on where they use the drugs, according to a study published in JNeurosci.

One in 10 people have traces of cocaine or heroin on their fingerprints
Scientists have found that drugs are now so prevalent that 13 percent of those taking part in a test were found to have traces of class A drugs on their fingerprints -- despite never using them.

Read More: Cocaine News and Cocaine Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.