Amylin Modulates the Mesolimbic Dopamine System to Control Energy Balance

Mietlicki‐Baase, Elizabeth G.; Reiner, David J.; Cone, Jackson J.; Olivos, Diana R.; McGrath, Lauren E.; Zimmer, Derek J.; Roitman, Mitchell F.; Hayes, Matthew R.

doi:10.1038/npp.2014.180

Cited by 87 publications

(117 citation statements)

References 72 publications

(96 reference statements)

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“…Thus, we argue that the present findings do not fall under the scope of calcium levels regulation, but they are a result of sCT's central action. Although there is no robust evidence that sCT crosses the blood-brain barrier effectively, there are data showing that peripheral sCT did not affect food intake in rats with a knocked down calcitonin receptor in the VTA but decreased food intake in control (Mietlicki-Baase et al 2015b). Moreover, a recent study showed that peripherally administered sCT decreased VTA-evoked phasic dopamine release in the NAc (Whiting et al 2017), supporting our notion that sCT acts centrally on the mesolimbic dopamine system to regulate dopamine neurotransmission.…”

Section: Discussionsupporting

confidence: 56%

“…In fact, amylin and sCT express their anorexigenic effects through central mechanisms involving the area postrema and the nucleus of the solitary tract (Lutz et al 2001a;Potes & Lutz 2010;Braegger et al 2014). Recent studies show that amylin receptors in the NAc, VTA and LDTg (Baisley & Baldo 2014;Mietlicki-Baase et al 2015a;Reiner et al 2017) and more specifically amylin receptors on ventral tegmental dopaminergic neurons mediate the effect of sCT on the control of energy balance (Mietlicki-Baase et al 2013;Mietlicki-Baase et al 2015b). Thus, amylin's action on the mesolimbic dopamine system suggests a potential role that extends beyond regulation of natural rewards, and tenuous evidence supports a possible amylinergic mediation of artificial rewards, such as alcohol.…”

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: 56%

Section: Introductionmentioning

confidence: 99%

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

2018

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“…These mechanisms certainly involve activation by proximal cues including orosensory stimulation, pre-absorptive mechanisms, and post-absorptive mechanisms [21,23,42,54,60]. Multiple hormones, among them ghrelin, insulin, amylin, and glucagon-like peptide 1, that are released peripherally interact either directly or indirectly with the mesolimbic dopamine pathway [15,[80][81][82][83][84]. Cells located both peripherally and centrally are able to respond to changes in glucose concentration including intestinal cells and dopamine neurons and their inputs [60,85,86].…”

Section: Mechanisms Of Dopamine Neuron Activation and Plasticitymentioning

confidence: 99%

The role of dopamine in the pursuit of nutritional value

McCutcheon

2015

Physiology & Behavior

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Acquiring enough food to meet energy expenditure is fundamental for all organisms. Thus, mechanisms have evolved to allow foods with high nutritional value to be readily detected, consumed, and remembered. Although taste is often involved in these processes, there is a wealth of evidence supporting the existence of taste-independent nutrient sensing. In particular, post-ingestive mechanisms arising from the arrival of nutrients in the gut are able to drive food intake and behavioural conditioning. The physiological mechanisms underlying these effects are complex but are believed to converge on mesolimbic dopamine signalling to translate post-ingestive sensing of nutrients into reward and reinforcement value. Discerning the role of nutrition is often difficult because food stimulates sensory systems and post-ingestive pathways in concert. Thus, in this mini-review, I discuss the various methods that may be used to study post-ingestive processes in isolation including sham-feeding, nonnutritive sweeteners, post-ingestive infusions, and pharmacological and genetic methods. Using this structure, I present the evidence that dopamine is sensitive to nutritional value of certain foods and examine how this affects learning about food, the role of taste, and the implications for human obesity.

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“…Leptin (NHPP) was dissolved in 0.01 M sodium bicarbonate. The selected doses of drugs were based on the literature (17,32,33).…”

Section: Subjectsmentioning

confidence: 99%

“…Recent studies have established the VTA as a physiologically and pharmacologically relevant site of action for the intake-suppressive effects of amylin (32,33). Furthermore, leptin has been shown to act independently in the VTA to induce hypophagia in a physiologically relevant manner (14,17).…”

mentioning

confidence: 99%

Cooperative interaction between leptin and amylin signaling in the ventral tegmental area for the control of food intake

Mietlicki‐Baase

Olivos

Jeffrey

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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Peripheral coadministration of amylin and leptin produces enhanced suppression of food intake and body weight, but the central nuclei mediating these effects remain unclear. Because each of these peptides controls feeding via actions at the ventral tegmental area (VTA), we tested the hypothesis that the VTA is a site of action for the cooperative effects of leptin and amylin on energy balance control. First, we show that intra-VTA injection of amylin and leptin at doses of each peptide that are effective in reducing food intake and body weight when administered separately produces an enhanced suppression of feeding when administered in combination. We also demonstrate that subthreshold doses of both amylin and leptin cause significant hypophagia and body weight loss when coadministered into the VTA. Additionally, we provide evidence that VTA amylin receptor blockade significantly attenuates the ability of intra-VTA leptin to reduce feeding and body weight gain. Together, these data provide the first evidence that the VTA mediates the interaction of amylin and leptin to cooperatively promote negative energy balance. obesity; mesolimbic; reward; islet amyloid polypeptide OBESITY REPRESENTS A PREVALENT, COSTLY HEALTH PROBLEM in the US and worldwide (11,43,44), yet effective noninvasive treatment options for this disease are extremely limited. Many pharmacotherapeutic strategies to date have attempted to treat obesity by targeting a single feeding-related neuroendocrine system, but the vast majority of these monotherapy approaches have failed to produce meaningful and sustained reductions in body weight (41). Therefore, attention has been turned to the notion that combination pharmacotherapies targeting more than one neuroendocrine feeding-relevant system may be more effective for the treatment of obesity (8,49,51).The pancreatic hormone amylin has been identified as a leading candidate for the development of combination pharmaceutical strategies for the treatment of obesity (47, 51). Amylin acts centrally to promote negative energy balance (24,50), and several reports have demonstrated that amylin can enhance the anorectic effects of other feeding-related signals in an additive if not synergistic manner (6,10,22,35). Of particular interest is that amylin interacts cooperatively with the adipose-derived hormone leptin to produce enhanced suppression of food intake and body weight (13,15). This amylinleptin interaction has been observed in rodents (13,42,48,56,57,59) and humans (46,48). Indeed, several studies demonstrate that peripheral administration of amylin and leptin (or agonists for their receptors) produces greater weight loss than either compound alone (48,56,59). Of critical importance for the treatment of obesity is the fact that although humans and rodent models exhibit reduced sensitivity to the energy balance effects of leptin in the obese state (1, 39), amylin appears to restore leptin sensitivity (13, 48, 56), thereby improving weight loss when amylin and leptin are coadministered.Although the body we...

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Amylin Modulates the Mesolimbic Dopamine System to Control Energy Balance

Cited by 87 publications

References 72 publications

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

The role of dopamine in the pursuit of nutritional value

Cooperative interaction between leptin and amylin signaling in the ventral tegmental area for the control of food intake

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