PLoS Biology (Jul 2018)

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

  • India A Reddy,
  • Nicholas K Smith,
  • Kevin Erreger,
  • Dipanwita Ghose,
  • Christine Saunders,
  • Daniel J Foster,
  • Brandon Turner,
  • Amanda Poe,
  • Vance L Albaugh,
  • Owen McGuinness,
  • Troy A Hackett,
  • Brad A Grueter,
  • Naji N Abumrad,
  • Charles Robb Flynn,
  • Aurelio Galli

DOI
https://doi.org/10.1371/journal.pbio.2006682
Journal volume & issue
Vol. 16, no. 7
p. e2006682

Abstract

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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.