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Orexin and motivation

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https://www.readbyqxmd.com/read/27909992/roles-for-orexin-hypocretin-in-the-control-of-energy-balance-and-metabolism
#1
Paulette B Goforth, Martin G Myers
The neuropeptide hypocretin is also commonly referred to as orexin, since its orexigenic action was recognized early. Orexin/hypocretin (OX) neurons project widely throughout the brain and the physiologic and behavioral functions of OX are much more complex than initially conceived based upon the stimulation of feeding. OX most notably controls functions relevant to attention, alertness, and motivation. OX also plays multiple crucial roles in the control of food intake, metabolism, and overall energy balance in mammals...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27909989/orexin-and-central-modulation-of-cardiovascular-and-respiratory-function
#2
Pascal Carrive, Tomoyuki Kuwaki
Orexin makes an important contribution to the regulation of cardiorespiratory function. When injected centrally under anesthesia, orexin increases blood pressure, heart rate, sympathetic nerve activity, and the amplitude and frequency of respiration. This is consistent with the location of orexin neurons in the hypothalamus and the distribution of orexin terminals at all levels of the central autonomic and respiratory network. These cardiorespiratory responses are components of arousal and are necessary to allow the expression of motivated behaviors...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27774604/distribution-physiology-and-pharmacology-of-relaxin-3-rxfp3-systems-in-brain
#3
REVIEW
Sherie Ma, Craig M Smith, Anna Blasiak, Andrew L Gundlach
Relaxin-3 is a member of a superfamily of structurally-related peptides that includes relaxin and insulin-like peptide hormones. Soon after the discovery of the relaxin-3 gene, relaxin-3 was identified as an abundant neuropeptide in brain with a distinctive topographical distribution within a small number of GABA neuron populations that is well conserved across species. Relaxin-3 is thought to exert its biological actions through a single class-A GPCR - relaxin-family peptide receptor 3 (RXFP3). Class-A comprises GPCRs for relaxin-3 and insulin-like peptide-5 and other peptides such as orexin and the monoamine transmitters...
October 23, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27771284/orexin-hypocretin-1-receptor-antagonism-reduces-ethanol-self-administration-and-reinstatement-selectively-in-highly-motivated-rats
#4
David E Moorman, Morgan H James, Elisabeth A Kilroy, Gary Aston-Jones
The orexin/hypocretin (ORX) system regulates motivation for natural rewards and drugs of abuse such as alcohol. ORX receptor antagonists, most commonly OX1R antagonists including SB-334867 (SB), decrease alcohol drinking, self-administration and reinstatement in both genetically-bred alcohol-preferring and outbred strains of rats. Importantly, levels of alcohol seeking and drinking in outbred rats are variable, as they are in humans. We have shown that OX1R antagonism selectively decreases homecage alcohol drinking in high-, but not low-alcohol-preferring rats...
January 1, 2017: Brain Research
https://www.readbyqxmd.com/read/27625592/nucleus-accumbens-shell-and-mpfc-but-not-insula-orexin-1-receptors-promote-excessive-alcohol-drinking
#5
Kelly Lei, Scott A Wegner, Ji Hwan Yu, Arisa Mototake, Bing Hu, Frederic W Hopf
Addiction to alcohol remains a major social and economic problem, in part because of the high motivation for alcohol that humans exhibit and the hazardous binge intake this promotes. Orexin-1-type receptors (OX1Rs) promote reward intake under conditions of strong drives for reward, including excessive alcohol intake. While systemic modulation of OX1Rs can alter alcohol drinking, the brain regions that mediate this OX1R enhancement of excessive drinking remain unknown. Given the importance of the nucleus accumbens (NAc) and anterior insular cortex (aINS) in driving many addictive behaviors, including OX1Rs within these regions, we examined the importance of OX1Rs in these regions on excessive alcohol drinking in C57BL/6 mice during limited-access alcohol drinking in the dark cycle...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27568806/aberrant-food-choices-after-satiation-in-human-orexin-deficient-narcolepsy-type-1
#6
Ruth Janke van Holst, Lisa van der Cruijsen, Petra van Mierlo, Gert Jan Lammers, Roshan Cools, Sebastiaan Overeem, Esther Aarts
STUDY OBJECTIVES: Besides influencing vigilance, orexin neurotransmission serves a variety of functions, including reward, motivation, and appetite regulation. As obesity is an important symptom in orexin-deficient narcolepsy, we explored the effects of satiety on food-related choices and spontaneous snack intake in patients with narcolepsy type 1 (n = 24) compared with healthy matched controls (n = 19). In additional analyses, we also included patients with idiopathic hypersomnia (n = 14) to assess sleepiness-related influences...
November 1, 2016: Sleep
https://www.readbyqxmd.com/read/27558790/differential-role-of-hypothalamic-orexin-hypocretin-neurons-in-reward-seeking-motivated-by-cocaine-versus-palatable-food
#7
Rémi Martin-Fardon, Gabrielle Cauvi, Tony M Kerr, Friedbert Weiss
Hypothalamic orexin/hypocretin (Orx/Hcrt) neurons are thought to mediate both food-reinforced behaviors and behavior motivated by drugs of abuse. However, the relative role of the Orx/Hcrt system in behavior motivated by food versus drugs of abuse remains unclear. This investigation addressed this question by contrasting hypothalamic Orx/Hcrt neuronal activation associated with reinstatement of reward seeking induced by stimuli conditioned to cocaine (COC) versus highly palatable food reward, sweetened condensed milk (SCM)...
August 24, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27540003/orexin-a-hypocretin-1-mediates-cocaine-seeking-behavior-in-the-posterior-paraventricular-nucleus-of-the-thalamus-via-orexin-hypocretin-receptor-2
#8
Alessandra Matzeu, Tony M Kerr, Friedbert Weiss, Rémi Martin-Fardon
Orexin/hypocretin (Orx/Hcrt) projections from the lateral hypothalamus to the paraventricular nucleus of the thalamus (PVT) are implicated in drug addiction. Specifically, the posterior section of the PVT (pPVT) innervates brain structures that modulate motivated behavior. This study investigated the role of pPVT-Orx/Hcrt transmission in cocaine-seeking behavior. Because the effects of Orx/Hcrt are mediated by two Orx/Hcrt receptors (Hcrt-r1 and Hcrt-r2), we examined the extent to which Hcrt-r1 and Hcrt-r2 are involved in Orx/Hcrt-induced cocaine seeking...
November 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27523303/orexin-1-receptor-blockade-suppresses-compulsive-like-alcohol-drinking-in-mice
#9
Kelly Lei, Scott A Wegner, Ji-Hwan Yu, F Woodward Hopf
Addiction is promoted by pathological motivation for addictive substances, and, despite extensive efforts, alcohol use disorders (AUDs) continue to extract a very high social, physical, and economic toll. Compulsive drinking of alcohol, where consumption persists even when alcohol is paired with negative consequences, is considered a particular obstacle for treating AUDs. Aversion-resistant alcohol intake in rodents, e.g. where rodents drink even when alcohol is paired with the bitter tastant quinine, has been considered to model some compulsive aspects of human alcohol consumption...
November 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27385732/ventral-tegmental-area-orexin-1-receptors-promote-palatable-food-intake-and-oppose-postingestive-negative-feedback
#10
Sarah J Terrill, Kellie M Hyde, Kristen E Kay, Hayden E Greene, Calyn B Maske, Amanda E Knierim, Jon F Davis, Diana L Williams
Hypothalamic orexin neurons project to numerous brain areas, including the ventral tegmental area (VTA), which is involved in motivation and food-seeking behavior. Here we address how exogenously administered orexin-A and endogenous orexin 1 receptor (OX1R) activation in the VTA affects feeding behavior. We hypothesized that orexin-A and OX1R antagonist SB334867 delivered to the VTA, at doses that were subthreshold for effect when injected into the ventricle, would affect intake of palatable foods in multiple test situations...
September 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27302606/hubs-and-spokes-of-the-lateral-hypothalamus-cell-types-circuits-and-behaviour
#11
Patricia Bonnavion, Laura E Mickelsen, Akie Fujita, Luis de Lecea, Alexander C Jackson
The hypothalamus is among the most phylogenetically conserved regions in the vertebrate brain, reflecting its critical role in maintaining physiological and behavioural homeostasis. By integrating signals arising from both the brain and periphery, it governs a litany of behaviourally important functions essential for survival. In particular, the lateral hypothalamic area (LHA) is central to the orchestration of sleep-wake states, feeding, energy balance and motivated behaviour. Underlying these diverse functions is a heterogeneous assembly of cell populations typically defined by neurochemical markers, such as the well-described neuropeptides hypocretin/orexin and melanin-concentrating hormone...
November 15, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/26851547/the-highly-selective-orexin-hypocretin-1-receptor-antagonist-gsk1059865-potently-reduces-ethanol-drinking-in-ethanol-dependent-mice
#12
Marcelo F Lopez, David E Moorman, Gary Aston-Jones, Howard C Becker
The orexin/hypocretin (ORX) system plays a major role in motivation for natural and drug rewards. In particular, a number of studies have shown that ORX signaling through the orexin 1 receptor (OX1R) regulates alcohol seeking and consumption. Despite the association between ORX signaling and motivation for alcohol, no study to date has investigated what role the ORX system plays in alcohol dependence, an understanding of which would have significant clinical relevance. This study was designed to evaluate the effect of the highly selective OX1R antagonist GSK1059865 on voluntary ethanol intake in ethanol-dependent and control non-dependent mice...
April 1, 2016: Brain Research
https://www.readbyqxmd.com/read/26845170/the-histaminergic-tuberomamillary-nucleus-is-involved-in-appetite-for-sex-water-and-amphetamine
#13
Marco Contreras, María E Riveros, Maricel Quispe, Cristián Sánchez, Guayec Perdomo, Fernando Torrealba, José L Valdés
The histaminergic system is one component of the ascending arousal system which is involved in wakefulness, neuroendocrine control, cognition, psychiatric disorders and motivation. During the appetitive phase of motivated behaviors the arousal state rises to an optimal level, thus giving proper intensity to the behavior. Previous studies have demonstrated that the histaminergic neurons show an earlier activation during the appetitive phase of feeding, compared to other ascending arousal system nuclei, paralleled with a high increase in arousal state...
2016: PloS One
https://www.readbyqxmd.com/read/26787120/orexin-in-rostral-hotspot-of-nucleus-accumbens-enhances-sucrose-liking-and-intake-but-scopolamine-in-caudal-shell-shifts-liking-toward-disgust-and-fear
#14
Daniel C Castro, Rachel A Terry, Kent C Berridge
The nucleus accumbens (NAc) contains a hedonic hotspot in the rostral half of medial shell, where opioid agonist microinjections are known to enhance positive hedonic orofacial reactions to the taste of sucrose ('liking' reactions). Within NAc shell, orexin/hypocretin also has been reported to stimulate food intake and is implicated in reward, whereas blockade of muscarinic acetylcholine receptors by scopolamine suppresses intake and may have anti-reward effects. Here, we show that NAc microinjection of orexin-A in medial shell amplifies the hedonic impact of sucrose taste, but only within the same anatomically rostral site, identical to the opioid hotspot...
July 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26598295/individual-differences-in-orexin-i-receptor-modulation-of-motivation-for-the-opioid-remifentanil
#15
Kirsten A Porter-Stransky, Brandon S Bentzley, Gary Aston-Jones
Orexin-1 receptors (Ox1Rs) have been implicated in the motivation for drugs of abuse. Here, we utilized a within-session behavioral-economics threshold procedure to screen for individual differences in economic demand for the ultra-short-acting opioid remifentanil and to test whether antagonism of Ox1Rs reduces remifentanil demand. The behavioral-economics procedure revealed robust individual differences in free consumption of remifentanil (Q0 parameter; hedonic set point). Rats with low baseline Q0 (low takers) displayed high demand elasticity (α parameter; reduced responding as drug price increased indicating low motivation for drug), whereas subjects with a higher Q0 (high takers) exhibit low demand elasticity (low α) by continuing to self-administer remifentanil despite increased cost (reflecting higher motivation for drug)...
November 24, 2015: Addiction Biology
https://www.readbyqxmd.com/read/26265304/excitatory-orexinergic-innervation-of-rat-nucleus-incertus-implications-for-ascending-arousal-motivation-and-feeding-control
#16
Anna Blasiak, Marcin Siwiec, Agnieszka Grabowiecka, Tomasz Blasiak, Anna Czerw, Ewa Blasiak, Alan Kania, Zenon Rajfur, Marian H Lewandowski, Andrew L Gundlach
Orexin/hypocretin peptides play a central role in the integrated control of feeding/reward and behavioural activation, principally via interactions with other neural systems. A brainstem area involved in behavioural activation is the nucleus incertus (NI), located in the posterior ventromedial central grey. Several studies have implicated NI in control of arousal/stress and reward/feeding responses. Orexin receptor mRNA expression identifies NI as a putative target of orexin modulation. Therefore, in this study we performed neural tract-tracing and immunofluorescence staining to characterise the orexinergic innervation of NI...
December 2015: Neuropharmacology
https://www.readbyqxmd.com/read/26177655/characterization-of-jnj-42847922-a-selective-orexin-2-receptor-antagonist-as-a-clinical-candidate-for-the-treatment-of-insomnia
#17
Pascal Bonaventure, Jonathan Shelton, Sujin Yun, Diane Nepomuceno, Steven Sutton, Leah Aluisio, Ian Fraser, Brian Lord, James Shoblock, Natalie Welty, Sandra R Chaplan, Zuleima Aguilar, Robin Halter, Anthony Ndifor, Tatiana Koudriakova, Michele Rizzolio, Michael Letavic, Nicholas I Carruthers, Timothy Lovenberg, Christine Dugovic
Dual orexin receptor antagonists have been shown to promote sleep in various species, including humans. Emerging research indicates that selective orexin-2 receptor (OX2R) antagonists may offer specificity and a more adequate sleep profile by preserving normal sleep architecture. Here, we characterized JNJ-42847922 ([5-(4,6-dimethyl-pyrimidin-2-yl)-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-yl-phenyl)-methanone), a high-affinity/potent OX2R antagonist. JNJ-42847922 had an approximate 2-log selectivity ratio versus the human orexin-1 receptor...
September 2015: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/26124708/lateral-hypothalamus-nucleus-accumbens-and-ventral-pallidum-roles-in-eating-and-hunger-interactions-between-homeostatic-and-reward-circuitry
#18
REVIEW
Daniel C Castro, Shannon L Cole, Kent C Berridge
The study of the neural bases of eating behavior, hunger, and reward has consistently implicated the lateral hypothalamus (LH) and its interactions with mesocorticolimbic circuitry, such as mesolimbic dopamine projections to nucleus accumbens (NAc) and ventral pallidum (VP), in controlling motivation to eat. The NAc and VP play special roles in mediating the hedonic impact ("liking") and motivational incentive salience ("wanting") of food rewards, and their interactions with LH help permit regulatory hunger/satiety modulation of food motivation and reward...
2015: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/26036709/concentration-dependent-activation-of-dopamine-receptors-differentially-modulates-gaba-release-onto-orexin-neurons
#19
Victoria Linehan, Robert B Trask, Chantalle Briggs, Todd M Rowe, Michiru Hirasawa
Dopamine (DA) and orexin neurons play important roles in reward and food intake. There are anatomical and functional connections between these two cell groups: orexin peptides stimulate DA neurons in the ventral tegmental area and DA inhibits orexin neurons in the hypothalamus. However, the cellular mechanisms underlying the action of DA on orexin neurons remain incompletely understood. Therefore, the effect of DA on inhibitory transmission to orexin neurons was investigated in rat brain slices using the whole-cell patch-clamp technique...
August 2015: European Journal of Neuroscience
https://www.readbyqxmd.com/read/25969666/suvorexant-the-first-orexin-receptor-antagonist-to-treat-insomnia
#20
Ashok K Dubey, Shailendra S Handu, Pramod K Mediratta
Primary insomnia is mainly treated with drugs acting on benzodiazepine receptors and a few other classes of drugs used for different co-morbidities. A novel approach to treat insomnia has been introduced recently, with the approval of suvorexant, the first in a new class of orexin receptor antagonists. Orexin receptors in the brain have been found to play an important role in the regulation of various aspects of arousal and motivation. The drugs commonly used for insomnia therapy to date, have often been associated with adverse effects, such as, day-time somnolence, amnesia, confusion, and gait disturbance, apart from the risk of dependence on chronic use...
April 2015: Journal of Pharmacology & Pharmacotherapeutics
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