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

Autor: Owen P. McGuinness, Brandon D. Turner, Daniel J. Foster, Dipanwita Ghose, Amanda Poe, Christine Saunders, India A. Reddy, Aurelio Galli, Naji N. Abumrad, Vance L. Albaugh, Brad A. Grueter, Nicholas K. Smith, Troy A. Hackett, Kevin Erreger, Charles R. Flynn
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Physiology
Dopamine
Bariatric Surgery
Choice Behavior
Nucleus Accumbens
Mice
Short Reports
Cocaine
Medicine and Health Sciences
Bile
Biology (General)
Sensitization
Mammals
Mice
Knockout
Behavior
Animal
Bile acid
General Neuroscience
Eukaryota
Gallbladder
G protein-coupled bile acid receptor
Body Fluids
Chemistry
medicine.anatomical_structure
Liver
Behavioral Pharmacology
Physical Sciences
Vertebrates
Knockout mouse
Anatomy
Signal transduction
General Agricultural and Biological Sciences
Signal Transduction
medicine.drug
medicine.medical_specialty
QH301-705.5
medicine.drug_class
Surgical and Invasive Medical Procedures
Motor Activity
Biology
Nucleus accumbens
Rodents
General Biochemistry
Genetics and Molecular Biology
Digestive System Procedures
03 medical and health sciences
Alkaloids
Mediator
Reward
Ileum
Recreational Drug Use
medicine
Animals
Pharmacology
General Immunology and Microbiology
Biological Locomotion
Chemical Compounds
Organisms
Biology and Life Sciences
Surgery
Gastrointestinal Tract
Mice
Inbred C57BL
030104 developmental biology
Biliary System
Amniotes
Digestive System
Zdroj: PLoS Biology
PLoS Biology, Vol 16, Iss 7, p e2006682 (2018)
ISSN: 1545-7885
Popis: 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.
Author summary Communication between the gut and the brain is increasingly being appreciated as influencing motivated behavior. The gut can influence brain function through secreted hormones traveling through the blood and entering the brain. We utilize a weight-loss surgery designed to elevate one class of circulating hormones, bile acids, to show their action in the brain and their role in modulating behaviors associated with the addictive properties of cocaine. This surgery reduces the reward-related behavior and the psychomotor effects of cocaine. Furthermore, we utilize a knockout mouse model to reveal that a specific bile acid receptor mediates some of the effects of bile acids over motivated behavior. Viral intervention studies localize this effect to a receptor population within the nucleus accumbens, a brain region central to the processing of reward. These findings identify a role for bile acids in blunting cocaine’s ability to alter brain function, generating novel and exciting directions for the treatment of cocaine abuse.
Databáze: OpenAIRE
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