The opioid beta-endorphin in the arcuate nucleus is involved in food intake

Wei, Q, Moore S, Watson S, Murphy G, Akil H
Society for Neuroscience. 2015.


The arcuate nucleus (Arc) of the hypothalamus is an important site for the central regulation of food intake, energy expenditure, and body weight. There are two classes of peptide-producing neuronal populations in the arcuate nucleus that are thought to exert opposing actions on feeding -- the orexigenic neurons that express NPY and AGRP, and the anorexigenic neurons that express POMC and CART. However, it should be noted that the gene encoding the precursor proopiomelanocortin (POMC) gives rise to two different groups of peptides, the melanocortins and beta-endorphin that are putatively co-released at axon terminals, and yet are thought to have opposing effects on feeding behavior. The role of melanocortins in the regulation of feeding and metabolism has been well defined by pharmacological and genetic methods, indicating an anorectic effect. On the other hand, pharmacological studies have generally indicated that opioids stimulate food intake, the opposite effect of melanocortins. While these components have been studied in isolation, we are unaware of studies that have selectively activated POMC neurons directly, thereby causing the release of both melanocortins and beta-endorphin while studying the impact on food intake. Thus, the current study used optogenetic stimulation to examine the effects of activating POMC neurons in the Arc on food intake in mice. In addition, we studied the impact on pain regulation, since this is one of the classical and well established effects of beta-endorphin on behavior. Surprisingly, activation of both dorsal and lateral Arc or of the lateral Arc alone led to a rapid and dramatic increase in food intake. This increased feeding could be largely blocked by pretreatment with the opioid receptor antagonist, naloxone, in a dose-dependent manner. Activation of both the dorsal and lateral Arc also induced an acute analgesic effect, which could be completely blocked by naloxone. In contrast, there was no analgesic effect of optogenetic stimulation in the lateral Arc. We also evaluated the cFos response following optogenetic stimulation in the Arc. Activation of the Arc resulted in an intensive cFos response in several brain regions. Importantly, the cFos response in these brain areas was abolished by pretreatment with naloxone. Together our findings demonstrate that the acute increase in food intake following activation of the arcuate is mediated by activation of the opioid system, and likely engages an extensive neural system in the brain. The exact physiological conditions that engage the appetite enhancing and appetite suppressive effects of POMC neurons remain to be fully understood.