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 alcohol‐consuming 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 alcohol‐consuming 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.
Highlights
Neuromedin U (NMU) is a highly conserved neuropeptide with pleiotropic functions
The present findings reveal that infusion of neuromedin U (NMU) into the nucleus accumbens (NAc) shell prevents acute effects of alcohol as primarily measured by alcohol‐ induced locomotor stimulation and formation of alcohol reward‐ dependent memory in mice
NMU infusion into NAc shell attenuates amphetamine induced locomotor sensitisation[25] and that the ability of acute cocaine to induce a locomotor stimulation is negatively associated with the expression of accumbal NMU receptors 2 (NMUR2).39 In addition, NMU into the NAc shell reduces alcohol intake in rats consuming alcohol for 12 weeks
Summary
Neuromedin U (NMU) is a highly conserved neuropeptide with pleiotropic functions. It is well‐known for its ability to reduce food intake and decrease the motivation to consume foods (for review[1]). Alcohol‐mediated behaviours are mandated via alcohol's ability to activate the nucleus accumbens (NAc) shell (for review[8]) This area contains NMU,[9] the expression of NMUR2 has been identified on GABA terminals in NAc,[4] and the NMUR2 protein has been detected within NAc.[10]. The VTA is a heterogeneous area, including the anterior (aVTA) as well as posterior part of the VTA When it comes to the aVTA, studies have found that alcohol infusion into this part increases accumbal dopamine in rats[16] and that nicotinic acetylcholine receptors regulate alcohol‐mediated behaviour in rodents.[17-19]. Food preference studies in mice were conducted, where chow and peanut butter intake was investigated following NMU infusion into NAc shell, aVTA, or LDTg. Collectively, the present study contributes to further understanding of the involvement of NMU in reward processes, with focus on striatal signalling
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
