A selective orexin-1 receptor antagonist reduces food consumption in male and female rats

Haynes, Andrea; Jackson, Brian A.; Chapman, Helen; Tadayyon, M.; Johns, Amanda; Porter, Roderick A.; Arch, Jonathan R.S.

doi:10.1016/s0167-0115(00)00199-3

Cited by 299 publications

(227 citation statements)

References 21 publications

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“…Several studies showed that orexin deficiency causes narcolepsy in humans and animals, implicating these hypothalamic neuropeptides in play a critical role in the regulation of sleep/wakefulness states [2][3][4][5][6] . However, orexins were initially recognized as regulators of feeding behavior, firstly because of their exclusive production in the lateral hypothalamic area (LHA), a region known as the "feeding center", and secondly because of their pharmacological activity; intracerebroventricular (ICV) injection of orexins induced feeding behavior in rats and mice 1,[7][8][9] . Recent studies suggested that further orexins play further roles in the coordination of emotion, energy homeostasis, reward system, drug addiction, and arousal [10][11][12][13][14][15][16][17] .…”

Section: Introductionmentioning

confidence: 99%

Roles of orexins in the regulation of body weight homeostasis

Sakurai

2014

Obesity Research & Clinical Practice

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running title, Orexin and body weight homeostasis key words, orexin, hypothalamus, feeding, arousal, body weight 1 AbstractLateral hypothalamic neuropeptides, orexins, have been recognized as one of the most important regulators of sleep/wakefulness states. Besides, these peptides are also regarded as an important factor that regulates feeding behavior, owing to their localization within the lateral hypothalamic area, the classic "feeding center", pharmacological activities, and the fact that prepro-orexin mRNA is upregulated when animals are fasted. This review summarizes the role of orexins in the regulation of feeding behavior and body weight homeostasis in relation to other systems that involve orexinergic neurotransmission.

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Section: Introductionmentioning

confidence: 99%

Roles of orexins in the regulation of body weight homeostasis

Sakurai

2014

Obesity Research & Clinical Practice

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“…Further to exhibiting a narcolepsy phenotype, OX knockout mice are also hypophagic compared with weight and age-matched littermates, indicating a role for OXs in modulating feeding and energy metabolism (Willie et al, 2001). Injection of OXA into the lateral ventricle of rats, during early light phase, induced a dose-related increase of food intake in rats (Sakurai et al, 1998), which was blocked by pre-treatment with the OX 1 R antagonist SB-334867 (Haynes et al, 2000;Rodgers et al, 2001). The role of OXs in reward-based food intake has been documented by a recent paper of Perello et al (2010), showing that the increase in the rewarding value of high-fat diet induced by ghrelin is OX-dependent; moreover, SB-334867 has been reported to inhibit high-fat food selfadministration (Nair et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Role of Orexin-1 Receptor Mechanisms on Compulsive Food Consumption in a Model of Binge Eating in Female Rats

Piccoli

Bonaventura

Cifani

et al. 2012

Neuropsychopharmacol

141

102

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Orexins (OX) and their receptors (OXR) modulate feeding, arousal, stress, and drug abuse. Neural systems that motivate and reinforce drug abuse may also underlie compulsive food seeking and intake. Therefore, the effects of GSK1059865, a dual OX 1 /OX 2 R antagonist were evaluated in a binge eating (BE) model in female rats. BE of highly palatable food (HPF) was evoked by three cycles of food restriction followed by stress, elicited by exposing rats to HPF, but preventing them from having access to it for 15 min. Pharmacokinetic assessments of all compounds were obtained under the same experimental conditions used for the behavioral experiments. Topiramate was used as the reference compound as it selectively blocks BE in rats and humans. Dose-related thresholds for sleep-inducing effects of the OXR antagonists were measured using polysomnography in parallel experiments. SB-649868 and GSK1059865, but not JNJ-10397049, selectively reduced BE for HPF without affecting standard food pellet intake, at doses that did not induce sleep. These results indicate, for the first time, a major role of OX 1 R mechanisms in BE, suggesting that selective antagonism at OX 1 R could represent a novel pharmacological treatment for BE and possibly other eating disorders with a compulsive component.

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“…Many brain regions/nuclei, including the arcuate nucleus (ARC), prefornical area, LHA, dorsomedial hypothalamic nucleus, paraventricular nucleus (PVN), VTA and nucleus accumbens, are effective sites for the injection of orexin to promote feeding [52] . The promotion effect is blocked significantly by central pretreatment with anti-orexin A antibodies and the highly selective OX1R antagonist SB-334867 [53,54] .…”

Section: Feeding and Energy Homeostasismentioning

confidence: 99%

Central functions of the orexinergic system

Zhang

Zhuang

et al. 2013

Neurosci. Bull.

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The neuropeptide orexin is synthesized by neurons exclusively located in the hypothalamus. However, these neurons send axons over virtually the entire brain and spinal cord and therefore constitute a unique central orexinergic system. it is well known that central orexin plays a crucial role in the regulation of various basic non-somatic and somatic physiological functions, including feeding, energy homeostasis, the sleep/wake cycle, reward, addiction, and neuroendocrine, as well as motor control. Moreover, the absence of orexin results in narcolepsy-cataplexy, a simultaneous somatic and non-somatic dysfunction. in this review, we summarize these central functions of the orexinergic system and associated diseases, and suggest that this system may hold a key position in somatic-non-somatic integration.

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A selective orexin-1 receptor antagonist reduces food consumption in male and female rats

Cited by 299 publications

References 21 publications

Roles of orexins in the regulation of body weight homeostasis

Roles of orexins in the regulation of body weight homeostasis

Role of Orexin-1 Receptor Mechanisms on Compulsive Food Consumption in a Model of Binge Eating in Female Rats

Central functions of the orexinergic system

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