Reversible suppression of food reward behavior by chronic mu-opioid receptor antagonism in the nucleus accumbens.
Overindulgence in easily available energy-dense palatable foods is thought to be an important factor in the current obesity epidemic but the underlying neural mechanisms are not well understood. Here we demonstrate that mu-opioid receptor signaling in the nucleus accumbens may be important. Protracted suppression of endogenous mu-opioid receptor signaling focused on the nucleus accumbens shell for several days by means of microinjected beta-funaltrexamine (BFNA) diminished both "liking" of sucrose, as indicated by fewer positive hedonic orofacial responses, and the incentive reinforcement value ("wanting") of a food reward, as indicated by lower completion speed and increased time being distracted in the incentive runway. BFNA-treatment also decreased responding to sucrose and corn oil in the brief access lick paradigm, a test measuring a combination of mainly taste-guided "liking" and low-effort "wanting", as well as 4 h intake of sucrose solution. These effects were not due to nonspecific permanent neuronal changes, as they were fully reversible. We conclude that endogenous mu-opioid signaling in the nucleus accumbens is necessary for the full display of palatable food-induced hyperphagia through mechanisms including hedonic, motivational, and reinforcement processes. Development of obesity could be the result of predisposing innate differences in these mechanisms or overstimulation of these mechanisms by external factors.
Shin
A C
AC
Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
Pistell
P J
PJ
Phifer
C B
CB
Berthoud
H R
HR
D000818:Animals; D001070:Appetitive Behavior / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009042:Motivation / Q000502:physiology; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000502:physiology*; D012054:Reinforcement, Psychology; D012201:Reward; D013395:Sucrose
D017450:Receptors, Opioid, mu; D013395:Sucrose; D009271:Naltrexone; C024524:beta-funaltrexamine