Central administration of the anorexigenic peptide neuromedin U decreases alcohol intake and attenuates alcohol‐induced reward in rodents

Vallöf, Daniel; Ulenius, Lisa; Egecioglu, Emil; Engel, Jörgen A.; Jerlhag, Elisabet

doi:10.1111/adb.12355

Cited by 19 publications

(39 citation statements)

References 47 publications

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“…Nevertheless, the effect of sCT is very pronounced in the 24-hour values in the high alcohol-consuming group, indicating different sensitivity of the two consuming groups to sCT in regard to alcohol intake regulation. In accordance are studies showing that central administration of neuromedin U dose dependently decreases alcohol intake in high but not in low alcohol-consuming rats (Vallof et al 2016b). Moreover, administration of a ghrelin antagonist reduced alcohol intake more robustly in rats voluntarily exposed to alcohol for 5 months instead of 2 (Landgren et al 2012).…”

Section: Discussionsupporting

confidence: 87%

“…More specifically, gut-brain peptides, which have been traditionally known to regulate food intake and energy balance (Ahima & Antwi 2008), seem to play a pivotal role in mediating the reinforcing properties of alcohol and other drugs of abuse Abizaid et al 2011;Clifford et al 2012;Egecioglu, Engel, & Jerlhag 2013a;Suchankova et al 2013a;Engel & Jerlhag 2014;Vadnie et al 2014;Vallof et al 2016c). Notably, ghrelin, glucagon-like peptide-1 and neuromedin U have been shown to alter alcohol-induced reward phenotypes by acting on the mesolimbic dopamine system (Kraus et al 2005;Leggio et al 2011;Jerlhag et al 2011b;Landgren et al 2012;Suchankova et al 2013b;Leggio et al 2014;Vallof et al 2016a;Vallof et al 2016b). Other hormones, for example, amylin, have been recently studied for their role to control energy balance through gut-brain axis regulation (Reda, Geliebter, & Pi-Sunyer 2002;Lutz 2009).…”

Section: Introductionmentioning

confidence: 99%

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Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

2018

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Alcohol expresses its reinforcing properties by activating areas of the mesolimbic dopamine system, which consists of dopaminergic neurons projecting from the ventral tegmental area to the nucleus accumbens. The findings that reward induced by food and addictive drugs involve common mechanisms raise the possibility that gut-brain hormones, which control appetite, such as amylin, could be involved in reward regulation. Amylin decreases food intake, and despite its implication in the regulation of natural rewards, tenuous evidence support amylinergic mediation of artificial rewards, such as alcohol. Therefore, the present experiments were designed to investigate the effect of salmon calcitonin (sCT), an amylin receptor agonist and analogue of endogenous amylin, on various alcohol-related behaviours in rodents. We showed that acute sCT administration attenuated the established effects of alcohol on the mesolimbic dopamine system, particularly alcohol-induced locomotor stimulation and accumbal dopamine release. Using the conditioned place preference model, we demonstrated that repeated sCT administration prevented the expression of alcohol's rewarding properties and that acute sCT administration blocked the reward-dependent memory consolidation. In addition, sCT pre-treatment attenuated alcohol intake in low alcohol-consuming rats, with a more evident decrease in high alcohol consumers in the intermittent alcohol access model. Lastly, sCT did not alter peanut butter intake, blood alcohol concentration and plasma corticosterone levels in mice. Taken together, the present data support that amylin signalling is involved in the expression of alcohol reinforcement and that amylin receptor agonists could be considered for the treatment of alcohol use disorder in humans.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

2018

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“…NMU receptors 2 (NMUR2) located in the arcuate nucleus, paraventricular nucleus, and dorsal raphe nucleus are key players for NMU's anorexigenic properties . An additional study has established that NMU infusion into the third ventricle attenuates both the acute effects of alcohol in mice and alcohol intake in a chronic rat model of alcohol use . The role of brain region specific NMUR2 in the acute and chronic effects of alcohol has not yet been explored.…”

Section: Introductionmentioning

confidence: 99%

“…We therefore hypothesise that activation of NMUR2 in NAc shell attenuates acute, as well as chronic effects of alcohol in rodents. Initial experiments explored the effects of NMU infusion into the NAc shell, on the ability of acute alcohol to cause locomotor simulation and to induce reward‐dependent memory retrieval in the conditioned place preference (CPP) model in mice, which are known to robustly respond to alcohol in these models . To further investigate the involvement of NAc shell as a mediator of the acute NMU‐alcohol link, we investigated changes in cFos expression, an immediate‐early gene and indicator of neuronal activity, following acute alcohol injection after central pretreatment of vehicle or NMU in rats.…”

Section: Introductionmentioning

confidence: 99%

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

2019

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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.

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“…While the effects of NMU on food intake and body weight have been evaluated (8, 11, 18–21), little consideration has been given to the reinforcing properties of food. However, NMU has recently been shown to regulate the reinforcement value of alcohol (22), and signaling between NMU and its CNS receptor, NMUR2, regulates preference for obesogenic food (9). Although NMU and food preference have been linked, the ability of NMU-NMUR2 signaling to modulate food reinforcement remains unstudied, and the specific neuroanatomical regions mediating the effects of NMU are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Regulation of motivation for food by neuromedin U in the paraventricular nucleus and the dorsal raphe nucleus

2016

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BACKGROUNDMotivation for high-fat food is thought to contribute to excess caloric intake in obese individuals. A novel regulator of motivation for food may be Neuromedin U (NMU), a highly-conserved neuropeptide which influences food intake. Although these effects of NMU have primarily been attributed to signaling in the paraventricular nucleus of the hypothalamus (PVN), NMU has also been found in other brain regions involved in both feeding behavior and motivation. We investigate the effects of NMU on motivation for food and food intake, and identify the brain regions mediating these effects.METHODSThe motivational state for a particular reinforcer (e.g., high-fat food) can be assessed using a progressive ratio schedule of reinforcement under which an increasing number of lever presses are required to obtain subsequent reinforcers. Here, we have employed a progressive ratio operant responding paradigm in combination with an assessment of cumulative food intake to evaluate the effects of NMU administration in rats, and identify the brain regions mediating these effects.RESULTSWe found that peripheral administration of NMU decreases operant responding for high-fat food in rats. Evaluation of Fos-like immunoreactivity in response to peripheral NMU indicated the PVN and dorsal raphe nucleus (DRN) as sites of action for NMU. NMU infusion into either region mimics the effects of peripheral NMU on food intake and operant responding for food. NMU-containing projections from the lateral hypothalamus (LH) to the PVN and DRN were identified as an endogenous source of NMU.CONCLUSIONSThese results identify the DRN as a site of action for NMU, demonstrate that the LH provides endogenous NMU to the PVN and DRN, and implicate NMU signaling in the PVN and DRN as a novel regulator of motivation for high-fat foods.

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Central administration of the anorexigenic peptide neuromedin U decreases alcohol intake and attenuates alcohol‐induced reward in rodents

Cited by 19 publications

References 47 publications

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

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

Regulation of motivation for food by neuromedin U in the paraventricular nucleus and the dorsal raphe nucleus

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