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

Academic Article

Abstract

  • © 2018 Reddy et al. http://creativecommons.org/licenses/by/4.0/. 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.
  • Authors

    Published In

  • PLoS Biology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Reddy IA; Smith NK; Erreger K; Ghose D; Saunders C; Foster DJ; Turner B; Poe A; Albaugh VL; McGuinness O
  • Volume

  • 16
  • Issue

  • 7