Incubation of feeding behavior is regulated by neuromedin U receptor 2 in the paraventricular nucleus of the hypothalamus

Abstract

A diet of energy-dense food, characterized mainly as a high-fat diet, leads to a persistent excessive consumption defined as overeating. According to the National Institute of Health, more than 2 in 3 adults in the United States are overweight or obese, straining our healthcare system with epidemic proportions. Diets that include abstaining from high-fat foods, ironically, result in an increase in motivation and craving for said high-fat foods, defined as an incubation effect because the behavior aids in developing overeating. Previously, we have shown that modulation of neuromedin U receptor 2 (NMUR2) in the paraventricular nucleus of the hypothalamus (PVN) results in increased food intake and motivation for energy-dense foods. Here, we continue our focus on NMUR2 in the PVN, but in relation to the incubation effect on craving for high-fat food. We employed a model for incubation of craving by having rats abstain from high-fat foods for 30 days before undergoing intake of fatty food on fixed ratio and progressive ratio schedules of reinforcement, and then assess their response to reactivity to cues. Using this model, we compared the feeding behaviors of rats that underwent an mRNA knockdown of the NMUR2 in the PVN to controls after both underwent a 30-day abstinence from high-fat foods. Our results show knockdown of NMUR2 in the PVN blocks the incubation of feeding behavior for food-related cues and high-fat foods.

Incubation of food craving in rats: A review

“…Rats responded in ten 6-hr daily sessions for intravenous cocaine and a tone+light cue. examined incubation of craving for complex foods and fats (e.g., standard or high-fat food pellets; Darling et al, 2016;Dingess et al, 2017;McCue, Kasper, & Hommel, 2019). * Indicates significant difference from Day 1, p < .05.…”

“…Serotonin 2C receptors have been associated with appetite (Halford & Harrold, 2012). In contrast to these negative effects, using a molecular manipulation, McCue et al (2019) reported that knockdown of neuromedin U receptor 2 in the paraventricular nucleus of the hypothalamus prevents incubation of high-fat food craving. These densities are hypothesized to be recruited to "stabilize" synapses and have been related to memory formation and retention (Slaker et al, 2018).…”

“…Copyright 2003 by the Society for Neuroscience. examined incubation of craving for complex foods and fats (e.g., standard or high-fat food pellets; Darling et al, 2016;Dingess et al, 2017;McCue, Kasper, & Hommel, 2019). An exhaustive review of the incubation literature reveals studies of incubation of drug craving that include incubation of food craving as a comparison condition.…”

“…These densities are hypothesized to be recruited to "stabilize" synapses and have been related to memory formation and retention (Slaker et al, 2018). In contrast to these negative effects, using a molecular manipulation, McCue et al (2019) reported that knockdown of neuromedin U receptor 2 in the paraventricular nucleus of the hypothalamus prevents incubation of high-fat food craving. Neuromedin is a neuropeptide involved in many behaviors, including feeding (Smith, Kasper, Ara, Anastasio, & Hommel, 2019;Vallöf, Kalafateli, & Jerlhag, 2019).…”

Cocaine-Evoked Locomotor Activity Negatively Correlates With the Expression of Neuromedin U Receptor 2 in the Nucleus Accumbens

“…NAc expression of NMU and NMUR2 in both sensitized and non-sensitized animals was quantified by RT-PCR (7500 Fast Real Time PCR system, Applied Biosystems). Rats were euthanized with Ketamine/Xylazine (Benzon et al, 2014 ; McCue et al, 2018 ), and the NAc was microdissected on ice (Paxinos and Watson, 2007 ). NAc tissue was homogenized, RNA was extracted (74104, Qiagen, Germantown, MD, USA) and converted to cDNA (170-8891, BioRad, Hercules, CA, USA).…”