Mu opioid receptor stimulation in the nucleus accumbens elevates fatty

Infusion of a mu opioid receptor (MOR) agonist into the nucleus accumbens (NAcc) drives voracious food intake, an effect hypothesized to occur through increased tastant palatability. While intake of many palatable foods is elevated by MOR stimulation, this manipulation has a preferential effect on fatty food ingestion. Consumption of high-fat foods is increased by NAcc MOR stimulation even in rats that prefer a carbohydrate-rich alternative under baseline conditions. This suggests that NAcc MOR stimulation may not simply potentiate palatability signals and raises the possibility that mechanisms mediating fat intake may be distinct from those underlying intake of other tastants. The present study was conducted to investigate the physiological mechanisms underlying the effects of NAcc MOR stimulation on fatty food intake. In Experiment 1, we analyzed lick microstructure in rats ingesting Intralipid to identify the changes underlying feeding induced by infusion of a MOR-specific agonist into the NAcc. MOR stimulation in the NAcc core but not shell increased burst duration and first-minute licks, while simultaneously increasing the rate and duration of Intralipid ingestion. These results suggest that MOR activation in the core increases Intralipid palatability and attenuates inhibitory post-ingestive feedback. In Experiment 2, we measured the effects of MOR stimulation in the NAcc core on consumption of non-nutritive Olestra. A MOR-specific agonist dose-dependently increased Olestra Articles in PresS. Am J Physiol Regul Integr Comp Physiol (May 4, 2011). doi:10.1152/ajpregu.00406.2010 Copyright © 2011 by the American Physiological Society. 2 intake, demonstrating that caloric signaling is not required for hyperphagia induced by NAcc MOR stimulation. Feeding induced by drug infusion in both Experiments 1 and 2 was blocked by a MOR antagonist. In Experiment 3, we determined if MOR activation in the NAcc core could attenuate satietyrelated signaling caused by infusion of the melanocortin agonist MTII into the 3 ventricle. Suppression of intake caused by MTII was reversed by MOR stimulation. Together, our results suggest that MOR stimulation in the NAcc core elevates fatty food intake through palatability mechanisms dependent on orosensory cues and suppression of satiety signals inhibiting food intake.