Binge-Type Eating in Rats is Facilitated by Neuromedin U Receptor 2 in the Nucleus Accumbens and Ventral Tegmental Area

Abstract

Binge-eating disorder (BED) is the most common eating disorder, characterized by rapid, recurrent overconsumption of highly palatable food in a short time frame. BED shares an overlapping behavioral phenotype with obesity, which is also linked to the overconsumption of highly palatable foods. The reinforcing properties of highly palatable foods are mediated by the nucleus accumbens (NAc) and the ventral tegmental area (VTA), which have been implicated in the overconsumption behavior observed in BED and obesity. A potential regulator of binge-type eating behavior is the G protein-coupled receptor neuromedin U receptor 2 (NMUR2). Previous research demonstrated that NMUR2 knockdown potentiates binge-type consumption of high-fat food. We correlated binge-type consumption across a spectrum of fat and carbohydrate mixtures with synaptosomal NMUR2 protein expression in the NAc and VTA of rats. Synaptosomal NMUR2 protein in the NAc demonstrated a strong positive correlation with binge intake of a “lower”-fat (higher carbohydrate) mixture, whereas synaptosomal NMUR2 protein in the VTA demonstrated a strong negative correlation with binge intake of an “extreme” high-fat (0% carbohydrate) mixture. Taken together, these data suggest that NMUR2 may differentially regulate binge-type eating within the NAc and the VTA.

Brain region‐specific neuromedin U signalling regulates alcohol‐related behaviours and food intake in rodents

“…It is also plausible that the behavioural responses to NMU into the posterior part of the VTA, where rats self‐administer alcohol, may be diverge. Another physiological role of NMU signalling within the aVTA is however most likely as we here show that the aVTA expresses NMU as well as NMUR2 and that NMUR2 was recently detected in the VTA . Indeed, both aVTA and LDTg were identified as novel areas, where NMU acts to reduce 4‐hour chow intake in mice, further confirming its anorexigenic properties .…”

“…Alcohol‐mediated behaviours are mandated via alcohol's ability to activate the nucleus accumbens (NAc) shell (for review). In addition, this area contains NMU, the expression of NMUR2 has been identified on GABA terminals in NAc, and the NMUR2 protein has been detected within NAc . We therefore hypothesise that activation of NMUR2 in NAc shell attenuates acute, as well as chronic effects of alcohol in rodents.…”

“…When it comes to the aVTA, studies have found that alcohol infusion into this part increases accumbal dopamine in rats and that nicotinic acetylcholine receptors herein regulate alcohol‐mediated behaviour in rodents . Recently, NMUR2 was detected in the VTA; however, neither NMU nor NMUR2 expression has been investigated in LDTg. Both aVTA and LDTg were identified as important areas for the gut‐brain peptide ghrelin to modulate alcohol drinking in mice .…”

Incubation of food craving in rats: A review

“…Finally, incubation of sucrose craving was not associated with changes in cortical (prelimbic, infralimbic, orbitofrontal) perineuronal net densities (Slaker, Barnes, Sorg, & Grimm, 2016). Neuromedin is a neuropeptide involved in many behaviors, including feeding (Smith, Kasper, Ara, Anastasio, & Hommel, 2019;Vallöf, Kalafateli, & Jerlhag, 2019). 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.…”

“…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). Fig.…”