Amylin Receptor Signaling in the Nucleus Accumbens Negatively Modulates mu-opioid-Driven Feeding

作者：Baisley Sarah K; Baldo Brian A^*

来源：Neuropsychopharmacology, 2014, 39(13): 3009-3017.

DOI：10.1038/npp.2014.153

Amylin is a peptide co-secreted with insulin that penetrates into the brain, and produces satiation-like effects via actions in the brainstem, hypothalamus, and mesencephalon. Little is known, however, about the effects of amylin in the nucleus accumbens shell (AcbSh), where a circumscribed zone of intense amylin receptor (AMY-R) binding overlaps reported mappings of a 'hotspot' for mu-opioid receptor (mu-OR) amplification of food reward. Here, the ability of intra-AcbSh AMY-R signaling to modulate ft-OR-driven feeding was explored. Amylin (1-30 ng) was administered with the, mu-OR agonist, D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) (0.25 mu g), directly into the AcbSh of ad libitum-maintained rats. Amylin dose-dependently reversed DAMGO-induced hyperphagia; 3 ng of amylin reduced DAMGO-mediated feeding by nearly 50%. This dose was, however, completely ineffective at altering DAMGO-induced feeding in the anterior dorsal striatum. Intra-AcbSh amylin alone (3-30 ng) modestly suppressed 10% sucrose intake in ad libitum-maintained rats, and chow in food-deprived rats, but only at the 30-ng dose. This result indicates that reversal of AcbSh DAMGO-induced feeding at a 10-fold lower dose was neither due to malaise nor motoric impairment. Finally, intra-AcbSh infusion of the AMY-R antagonist, AC187 (20 mu g), significantly attenuated the ability of prefeeding to suppress DAMGO-induced food intake, with no effects in non-prefed rats. Hence, AMY-R signaling negatively modulates mu-OR-mediated appetitive responses at the level of the AcbSh. The results with AC187 indicate that endogenous AMY-R transmission in the AcbSh curtails opioid function in the postprandial period, suggesting a novel pathway for peripheral-central integration in the control of appetitive motivation and opioid reward.

• 出版日期2014-12