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

Abstract

Albeit neuromedin U (NMU) attenuates alcohol-mediated behaviours, its mechanisms of action are poorly defined. Providing that the behavioural effects of alcohol are processed within the nucleus accumbens (NAc) shell, anterior ventral tegmental area (aVTA), and laterodorsal tegmental area (LDTg), we assessed the involvement of NMU signalling in the aforementioned areas on alcohol-mediated behaviours in rodents. We further examined the expression of NMU and NMU receptor 2 (NMUR2) in NAc and the dorsal striatum of high compared with low alcoholconsuming rats, as this area is of importance in the maintenance of alcohol use disorder (AUD). Finally, we investigated the involvement of NAc shell, aVTA and LDTg in the consumption of chow and palatable peanut butter, to expand the link between NMU and reward-related behaviours. We demonstrated here, that NMU into the NAc shell, but not aVTA or LDTg, blocked the ability of acute alcohol to cause locomotor stimulation and to induce memory retrieval of alcohol reward, as well as reduced peanut butter in mice. In addition, NMU into NAc shell decreased alcohol intake in rats. On a molecular level, we found increased NMU and decreased NMUR2 expression in the dorsal striatum in high compared with low alcoholconsuming rats. Both aVTA and LDTg, rather than NAc shell, were identified as novel sites of action for NMU's anorexigenic properties in mice based on NMU's ability to selectively reduce chow intake when injected to these areas. Collectively, these data indicate that NMU signalling in different brain areas selectively modulates different behaviours.

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.…”

Cocaine has some effect on neuromedin U expressing neurons related to the brain reward system

“…Moreover, a genome-wide allelic association study shows that a single nucleotide polymorphism in NMUR2 is associated with alcohol abuse in humans [18]. Furthermore, intra-NAc administration of NMU prevents non-sensitized cocaine evoked activity [15], selectively reduced palatable and rewarding peanut butter consumption [19]. These evidences support the role of the NMU system in reward processes.…”

“…Over the last decade, some of the appetite regulatory peptides, such as ghrelin, glucagon-like peptide-1 (GLP1), neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opiomelanocortin (POMC), and cocaine-amphetamine regulated transcript (CART), were reported to have a pivotal role in the process of drug reinforcement or brain reward system [13,24,25]. NMU and NMUR2, one of the NMU receptors mainly expressed in the central nervous system, have recently been also shown to regulate the reinforcement value of amphetamine-evoked locomotion [16], alcohol [17] and preference for obesogenic, palatable food [19,26].…”

“…Several studies have shown a link between the NMU system and the brain reward system [13,14,15,16,17,18,19]. NMU is highly expressed in the area associated with the brain reward system, including the nucleus accumbens (NAc) [13,14].…”