Unknown

Dataset Information

0

Bile diversion, a bariatric surgery, and bile acid signaling reduce central cocaine reward.


ABSTRACT: The gut-to-brain axis exhibits significant control over motivated behavior. However, mechanisms supporting this communication are poorly understood. We reveal that a gut-based bariatric surgery chronically elevates systemic bile acids and attenuates cocaine-induced elevations in accumbal dopamine. Notably, this surgery reduces reward-related behavior and psychomotor sensitization to cocaine. Utilizing a knockout mouse model, we have determined that a main mediator of these post-operative effects is the Takeda G protein-coupled bile acid receptor (TGR5). Viral restoration of TGR5 in the nucleus accumbens of TGR5 knockout animals is sufficient to restore cocaine reward, centrally localizing this TGR5-mediated modulation. These findings define TGR5 and bile acid signaling as pharmacological targets for the treatment of cocaine abuse and reveal a novel mechanism of gut-to-brain communication.

SUBMITTER: Reddy IA 

PROVIDER: S-EPMC6061973 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

2015-05-13 | E-GEOD-68812 | biostudies-arrayexpress
2015-05-13 | GSE68812 | GEO
| S-EPMC4518285 | biostudies-literature
| S-EPMC4587641 | biostudies-literature
2024-07-21 | GSE262065 | GEO
| PRJEB39382 | ENA
| PRJNA1041054 | ENA
| PRJEB28869 | ENA
| S-EPMC4783581 | biostudies-other
| S-EPMC5315559 | biostudies-literature