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

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

in Acids / Anesthesiology / Animals / Bariatric Surgery / Behavior, Animal / Bile / Bile - metabolism / Bile acids / Biology and Life Sciences / Biophysics / Brain / Choice Behavior - drug effects / Cocaine / Cocaine - pharmacology / Dopamine / Dopamine - metabolism / Drug abuse / Food / Gallbladder / Gallbladder - metabolism / Gastrointestinal surgery / Health aspects / Homeostasis / Ileum - metabolism / Male / Medicine and Health Sciences / Mice, Inbred C57BL / Mice, Knockout / Motivation / Motor Activity - drug effects / Narcotics / Neurosciences / Nucleus accumbens / Nucleus Accumbens - metabolism / Obesity / Pharmacology / Physical Sciences / Physiology / Proteins / Reinforcement / Restoration / Reward / Short Reports / Signal Transduction / Signaling / Small intestine / Students / Supervision / Surgery

2018

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

2018

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2018

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Journal Article

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

Smith, Nicholas K.,

Albaugh, Vance L.,

Abumrad, Naji N.,

McGuinness, Owen,

Turner, Brandon,

Galli, Aurelio,

Saunders, Christine,

Hackett, Troy A.,

Reddy, India A.,

Flynn, Charles Robb,

Poe, Amanda,

Grueter, Brad A.,

Ghose, Dipanwita,

Foster, Daniel J.,

Erreger, Kevin

2018

Overview

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.

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Publisher

Public Library of Science,Public Library of Science (PLoS)

Subject

/ Animals

/ Bile