Reversible suppression of food reward behavior by chronic mu-opioid receptor antagonism in the nucleus accumbens

Abstract

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.

Keywords: hedonic value; obesity; reward; taste reactivity; ventral striatum; working for food.

Fig. 1

Experimental design. Note that rats initially treated with BFNA on days 0 and 4, received an injection of saline on day 30, while rats initially treated with saline received BFNA on day 30.

Fig. 2

‘Liking’ as measured by the taste reactivity test. Rats were tested 2–8 days (active treatment, A) and 16–18 days (recovery, B) after the first injection of saline (n = 6) or BFNA (n = 6) into the nucleus accumbens shell. The number of positive orofacial hedonic reactions was counted after ingesting a small amount of sucrose solution (<200 µl) and averaged over 3 bouts for each concentration. ‘Liking’ of all three concentrations was significantly (* p < 0.05) reduced during active treatment with BFNA compared to saline, but was not different during the recovery from treatment.

Fig. 3

Incentive runway performance as a measure of ‘wanting’. A: Nucleus accumbens BFNA-treatment significantly (* p < 0.05) reduced completion speed up to 8 days after the first BFNA injection. At 14 days after the first injection, completion speed was no longer different between saline and BFNA-treated rats. B: Net running speed was not different, indicating that BFNA-treatment did not affect motor performance per se. C: Distractions including latency to leave the start box, pauses along the runway, and reversals, were significantly (* p < 0.05) longer in duration after BFNA-treatment.

Fig. 4

Brief access lickometer responding as a measure of combined ‘liking’ and taste-guided ‘wanting’, 2–6 days (active treatment, A,B) and 16–18 days (recovery, C,D) after saline (n =6) or BFNA (n =6) treatment. Nucleus accumbens BFNA-treatment significantly (* p < 0.05) reduced responding for middle range of sucrose concentrations (A) and for the highest concentration of corn oil emulsion (B). Responding for both tastants was no longer different after recovery.

Fig. 5

Sucrose intake before and after nucleus accumbens administration of BFNA (closed bars, n = 6) or vehicle (open bars, n = 6). 20% sucrose solution was made available for 4 h during the light period in ad libitum chow fed rats. * p < 0.05.

Fig. 6

Histological verification of injection sites. Estimated locations of injector cannula tips for saline – treated (open circles) and BFNA-treated (closed circles) rats, based on recovery of blue dye injected at sacrifice. Sites are superimposed on successive plates 11, 12, and 13 of the Paxinos and Watson stereotaxic atlas (Paxinos and Watson, 1986).