Chronic suppression of mu-opioid receptor signaling in the nucleus accumbens attenuates development of diet-induced obesity in rats

OBJECTIVE: To test the hypothesis that mu-opioid receptor signaling in the nucleus accumbens contributes to hedonic (over)eating and obesity. To investigate the effects of chronic mu-opioid antagonism in the nucleus accumbens core or shell on intake of a palatable diet, and the development of diet-induced obesity in rats. METHODS AND DESIGN: Chronic blockade of mu-opioid receptor-signaling in the nucleus accumbens core or shell was achieved by means of repeated injections (every 4–5 days) of the irreversible receptor antagonist β-Funaltrexamine (BFNA) over 3–5 weeks. The diet consisted of either a choice of high-fat chow, chocolate-flavored Ensure, and regular chow (each nutritionally complete), or regular chow only. Intake of each food item, body weight, and body fat mass were monitored throughout the study. RESULTS: BFNA injections aimed at either the core or shell of the nucleus accumbens resulted in significantly attenuated intake of palatable diet, body weight gain, and fat accretion, compared with vehicle control injections. BFNA in the core did not significantly change these parameters in chow-fed control rats. BFNA in the core and shell differentially affected intake of the two palatable food items: in the core BFNA significantly reduced intake of high-fat, but not of Ensure, whereas in the shell, it significantly reduced intake of Ensure, but not of high-fat, compared with vehicle-treatment. CONCLUSIONS: Endogenous mu-opioid receptor-signaling in the nucleus accumbens core and shell is necessary for palatable diet-induced hyperphagia and obesity to fully develop in rats. Sweet and non-sweet fatty foods may be differentially processed in subcomponents of the ventral striatum.