5‐HT<sub>2C</sub> receptor activation inhibits appetitive and consummatory components of feeding and increases brain c‐<i>fos</i> immunoreactivity in mice

Somerville, Elizabeth M.; Horwood, Julia; Lee, Michelle D.; Kennett, Guy A.; Clifton, Peter G.

doi:10.1111/j.1460-9568.2007.05567.x

Cited by 70 publications

(43 citation statements)

References 42 publications

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Section: -Ht Receptors and Feedingmentioning

confidence: 95%

“…Experimental evidence exists that 5-HT2C agonists do not only inhibit food intake, e.g. the consummatory component of feeding behaviour, but also the preceding appetitive phase, which is not yet food related [82,359]. Combining the 5-HT2C/1B agonist mCPP with the CB1 antagonist/partial agonist rimonabant synergistically reduced motivated feeding behaviour in an operant paradigm in mice [360].…”

Section: Serotonin and The Pharmacotherapy Of Obesitymentioning

confidence: 99%

“…Acceleration of the BSS by mCPP has been reported both for rats and mice [72, 73, 80], but not in a recent rat study [81]. Activation of the 5-HT2C receptor in mice, using the selective agonist VER2379, accelerated behavioural satiety, but induced also a reduction of non-food reinforced appetitive responding [82].Being complementary to, and in combination with pharmacological approaches, transgenic techniques provided further evidence for the involvement of 5-HT1B and 5-HT2C receptors in physiological satiety. A 5-HT2C receptor knockout was accompanied by hyperphagia leading to hyperglycaemia, insulin resistance and late-onset obesity [83,84].…”

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confidence: 96%

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Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

270

167

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Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and 'true' 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 IntroductionWhat are the behavioural and physiological mechanisms that promote satiety? How is satiety defined? Satiety can be seen as a behavioural state which arises from food consumption and suppresses the initiation of eating for a particular period of time [1]. This description alone suggests a high degree of complexity as peripheral post-ingestive and post-absorptive signals need to be relayed to the brain where they are integrated with other signals to produce (or not) the behavioural state called satiety. The state of satiety is brought about a process called satiation, where sensory, cognitive and early post-ingestive mechanisms bring feeding to a halt and thus stopping a meal. Promoting satiation alone must not necessarily lead to reduced total food intake as the frequency of meals could be increased subsequently. Many peripheral and brain mechanisms have been identified that are involved in the expression satiety and it has been suggested that serotonin accelerates satiation and prolongs satiety [2]. In the following, we will review the role of serotonin in satiety in more detail 1 . The reader will see that, despite immense progress made during the last years, the field is still far from being resolved.As serotonin (5-Hydroxytryptamine; 5-HT) is a phylogenetically old neurotransmitter, various functions had time to evolve in different phyla, but maybe also in different species. 5-HT receptors exist in animal cells for millions of years and they are as old as adrenoreceptors ore some peptide receptors, possibly even older [5,6]. Even in invertebrates such as molluscs (Aplysia californica) and annelids (Hirudo medicinalis), 5-HT might functionally be related to food intake [7]. 5-HT is involved in feeding even in the honeybee where it has separate effects in the gut and in the insect brain [8]. In general, however, 5-HT seems rather to be involved in appetitive behaviours in invertebrates whereas it has more of a satiating effect in vertebrates [9]. In general, 5-HT neurons seem to be more extensively distributed throughout the body in lower animals than in higher animals including mammals where 5-HT neurones...

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Section: -Ht Receptors and Feedingmentioning

confidence: 95%

Section: Serotonin and The Pharmacotherapy Of Obesitymentioning

confidence: 99%

mentioning

confidence: 96%

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Serotonin controlling feeding and satiety

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2015

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“…Interestingly, serotonergic signaling has since long been known to be involved in controlling food intake and to impact on satiety [28][29][30][31][32][33][34][35][36][37][38] . Individuals with normal regulated brain serotonin (5-hydroxytryptamine, 5-HT) levels are more easily satiated and display a better control over carbohydrate cravings inhibiting sugar intake more readily 39,40 .…”

Section: Introductionmentioning

confidence: 99%

Ghrelin’s Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction

Schellekens¹,

Francesco²,

Kandil³

et al. 2015

ACS Chem. Neurosci.

108

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Understanding the intricate pathways modulating appetite and subsequent food intake is of particular importance considering the rise in obesity incidence across the globe. The serotonergic system, specifically the 5-HT2C receptor, has shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor wellknown for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signalling is not due to coupling to GαS, as no increase in cAMP signalling is observed. Next, flowcytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor.In addition, we demonstrate co-localized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic-and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signalling is blocked, ghrelin's orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into biological significant modulation of ghrelin's orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management. ACS Paragon Plus Environment ACS Chemical Neuroscience 5

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“…Extracellular concentrations of serotonin and its metabolite 5-HIAA increase in rats' brains during spontaneous meals (44). The serotonin agonist fenfluramine, which both releases synaptic serotonin and blocks serotonin reuptake (14, 21), inhibits eating in rats by reducing meal size without affecting meal frequency or causing adverse behavioral effects (8,9,16,29,52). The most extensively studied serotonin receptor in relation to the control of eating is the serotonin 2C receptor (2CR) (51, 56).…”

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confidence: 99%

Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors

Asarian

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Asarian L. Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors. Am J Physiol Regul Integr Comp Physiol 296: R51-R56, 2009. First published November 12, 2008 doi:10.1152/ajpregu.90655.2008.-To investigate the role of serotonin 2C receptors (2CR), which are expressed only in the central nervous system, in the satiating actions of the gut peptides CCK and glucagon-like peptide 1 (GLP-1), we examined 1) the effect of null mutations of serotonin 2CR (2CR KO) on the eating-inhibitory potencies of dark-onset intraperitoneal injections of 0.9, 1.7, or 3.5 nmol/kg (1, 2, or 4 g/kg) CCK and 100, 200, and 400 nmol/kg (33, 66, or 132 g/kg) GLP-1, and 2) the effects of intraperitoneal injections of 1.7 nmol//kg CCK and 100 nmol/kg GLP-1 on neuronal activation in the brain, as measured by c-Fos expression. All CCK and GLP-1 doses decreased 30-min food intake in wild-type (WT) mice, but none of them did in 2CR KO mice. CCK increased the number of cells expressing c-Fos in the nucleus tractus solitarii (NTS) of WT, but not 2CR KO mice. CCK induced similar degrees of c-Fos expression in the paraventricular (PVN) and arcuate (Arc) nuclei of the hypothalamus of both genotypes. GLP-1, on the other hand, increased c-Fos expression similarly in the NTS of both genotypes and increased c-Fos expression more in the PVN and Arc of 2CR KO mice, but not WT mice. These results indicate that serotonin signaling via serotonin 2CR is necessary for the full satiating effects of CCK and GLP-1. In addition, they suggest that the satiating effects of the two peptides are mediated by different neural mechanisms. endocrine; eating; hormone; neural; immunocytochemistry; 5HT ON THE BASIS OF FULFILLMENT of criteria for endocrine satiation signals initially proposed by Gibbs et al. (20), intestinal CCK and GLP-1 are now considered to be physiological controls of eating (4,10,19,32). Both hormones are released during meals, and premeal administration of doses producing plasma hormone levels that are similar to prandial levels is sufficient to inhibit meal size in the absence of adverse effects in humans. Furthermore, administration of CCK 1 receptor antagonists in humans or rats, or GLP-1 receptor antagonists in rats, increases food intake (Williams D, personal communication); CCK 1 receptor antagonists also block the satiating effects of CCK secretagogues in humans and rats. Although the understanding of the roles of these peptides in physiology of eating has increased tremendously in the last two decades (19,39,41,54), the brain mechanisms underlying their effects are still unclear.Serotonin appears to be a key neurotransmitter in the central mediation of eating, including the control of meal size. Extracellular concentrations of serotonin and its metabolite 5-HIAA increase in rats' brains during spontaneous meals (44). The serotonin agonist fenfluramine, which both releases synaptic serotonin and blocks serotonin reuptake (14, 21), inhibits eating in rats by reducing meal size without affectin...

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5‐HT_2C receptor activation inhibits appetitive and consummatory components of feeding and increases brain c‐fos immunoreactivity in mice

Cited by 70 publications

References 42 publications

Serotonin controlling feeding and satiety

Serotonin controlling feeding and satiety

Ghrelin’s Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction

Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors

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5‐HT2C receptor activation inhibits appetitive and consummatory components of feeding and increases brain c‐fos immunoreactivity in mice

Cited by 70 publications

References 42 publications

Serotonin controlling feeding and satiety

Serotonin controlling feeding and satiety

Ghrelin’s Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction

Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors

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5‐HT_2C receptor activation inhibits appetitive and consummatory components of feeding and increases brain c‐fos immunoreactivity in mice