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

Reddy IA, Smith NK, Erreger K, Ghose D, Saunders C, Foster DJ, Turner B, Poe A, Albaugh VL, McGuinness O, Hackett TA, Grueter BA, Abumrad NN, Flynn CR, Galli A
PLoS Biol. 2018 16 (7): e2006682

PMID: 30048457 · PMCID: PMC6061973 · DOI:10.1371/journal.pbio.2006682

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.

MeSH Terms (16)

Animals Bariatric Surgery Behavior, Animal Bile Choice Behavior Cocaine Dopamine Gallbladder Ileum Male Mice, Inbred C57BL Mice, Knockout Motor Activity Nucleus Accumbens Reward Signal Transduction

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