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Orexin and motivation

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https://www.readbyqxmd.com/read/28178514/projection-target-defined-effects-of-orexin-and-dynorphin-on-vta-dopamine-neurons
#1
Corey Baimel, Benjamin K Lau, Min Qiao, Stephanie L Borgland
Circuit-specific signaling of ventral tegmental area (VTA) dopamine neurons drives different aspects of motivated behavior, but the neuromodulatory control of these circuits is unclear. We tested the actions of co-expressed lateral hypothalamic peptides, orexin A (oxA) and dynorphin (dyn), on projection-target-defined dopamine neurons in mice. We determined that VTA dopamine neurons that project to the nucleus accumbens lateral shell (lAcbSh), medial shell (mAcbSh), and basolateral amygdala (BLA) are largely non-overlapping cell populations with different electrophysiological properties...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28025575/patterned-feeding-induces-neuroendocrine-behavioral-and-genetic-changes-that-promote-palatable-food-intake
#2
S Sirohi, A Van Cleef, J F Davis
BACKGROUND: Selection of a healthy diet is the cornerstone for treating obesity and metabolic disease. Unfortunately, the majority of diets fail leading to weight regain and in some cases, pathological feeding behavior. We hypothesize that alternating bouts of caloric overconsumption and caloric restriction, behavioral manifestations of dieting, induce neuroendocrine, behavioral, and genetic changes that promote future bouts of palatable food intake. METHODS: To test this hypothesis, we subjected male Long Evans rats to a HFD feeding paradigm that induced a pattern of caloric overconsumption and caloric restriction...
December 27, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28012090/a-decade-of-orexin-hypocretin-and-addiction-where-are-we-now
#3
Morgan H James, Stephen V Mahler, David E Moorman, Gary Aston-Jones
One decade ago, our laboratory provided the first direct evidence linking orexin/hypocretin signaling with drug seeking by showing that activation of these neurons promotes conditioned morphine-seeking behavior. In the years since, contributions from many investigators have revealed roles for orexins in addiction for all drugs of abuse tested, but only under select circumstances. We recently proposed that orexins play a fundamentally unified role in coordinating "motivational activation" under numerous behavioral conditions, and here we unpack this hypothesis as it applies to drug addiction...
December 24, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27997037/descending-projections-from-the-basal-forebrain-to-the-orexin-neurons-in-mice
#4
Lindsay J Agostinelli, Loris L Ferrari, Carrie E Mahoney, Takatoshi Mochizuki, Bradford B Lowell, Elda Arrigoni, Thomas E Scammell
The orexin (hypocretin) neurons play an essential role in promoting arousal, and loss of the orexin neurons results in narcolepsy, a condition characterized by chronic sleepiness and cataplexy. The orexin neurons excite wake-promoting neurons in the basal forebrain (BF), and a reciprocal projection from the BF back to the orexin neurons may help promote arousal and motivation. The BF contains at least three different cell types (cholinergic, glutamatergic, and GABAergic neurons) across its different regions (medial septum, diagonal band, magnocellular preoptic area, and substantia innominata)...
December 20, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27909992/roles-for-orexin-hypocretin-in-the-control-of-energy-balance-and-metabolism
#5
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
#6
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
#7
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 GABAergic 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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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