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Orexin and motivation

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https://www.readbyqxmd.com/read/29740277/hedonic-eating-and-the-delicious-circle-from-lipid-derived-mediators-to-brain-dopamine-and-back
#1
REVIEW
Roberto Coccurello, Mauro Maccarrone
Palatable food can be seductive and hedonic eating can become irresistible beyond hunger and negative consequences. This is witnessed by the subtle equilibrium between eating to provide energy intake for homeostatic functions, and reward-induced overeating. In recent years, considerable efforts have been devoted to study neural circuits, and to identify potential factors responsible for the derangement of homeostatic eating toward hedonic eating and addiction-like feeding behavior. Here, we examined recent literature on "old" and "new" players accountable for reward-induced overeating and possible liability to eating addiction...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29703996/knockdown-of-hypocretin-attenuates-extended-access-of-cocaine-self-administration-in-rats
#2
Brooke E Schmeichel, Alessandra Matzeu, Pascale Koebel, Leandro F Vendruscolo, Harpreet Sidhu, Roxana Shahryari, Brigitte L Kieffer, George F Koob, Rémi Martin-Fardon, Candice Contet
The hypocretin/orexin (HCRT) neuropeptide system regulates feeding, arousal state, stress responses, and reward, especially under conditions of enhanced motivational relevance. In particular, HCRT neurotransmission facilitates drug-seeking behavior in circumstances that demand increased effort and/or motivation to take the drug. The present study used a shRNA-encoding adeno-associated viral vector to knockdown Hcrt expression throughout the dorsal hypothalamus in adult rats and determine the role of HCRT in cocaine self-administration...
April 6, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29684475/orexin-a-in-the-ventral-tegmental-area-enhances-saccharin-induced-conditioned-flavor-preference-the-role-of-d1-receptors-in-central-nucleus-of-amygdala
#3
Severiano Risco, Cristina Mediavilla
In industrialized societies, food intake is largely determined by its hedonic characteristics, which can be modified by our experience via taste learning. In this learning, the hedonic value of a neutral flavor changes after its association with a motivationally significant stimulus. Experiment 1 analyzes the effect of orexin administration (53 and 107 ng) in the ventral tegmental area (VTA) on hedonic intake through acquisition of a flavor-taste preference and a flavor-taste aversion. Accordingly, animals underwent four one-bottle acquisition sessions with unilateral application of orexin-A or saline in the VTA at 10 min before a 15-min flavor intake period...
April 20, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29623046/functional-changes-induced-by-orexin-a-and-adiponectin-on-the-sympathetic-parasympathetic-balance
#4
Antonietta Messina, Marcellino Monda, Anna Valenzano, Giovanni Messina, Ines Villano, Fiorenzo Moscatelli, Giuseppe Cibelli, Gabriella Marsala, Rita Polito, Maria Ruberto, Marco Carotenuto, Vincenzo Monda, Andrea Viggiano, Aurora Daniele, Ersilia Nigro
Obesity and lifestyle-related diseases are major problems faced by people in developed nations. Although exercise training prevents the progression of diabetes and obesity, the motivation for exercise is generally low in obese animals and humans. The autonomic nervous system (SNA) plays a crucial role in the regulation of eating behavior. Moreover, the SNA is involved in the body temperature regulation that is strictly related to body weight control, in accordance with the "thermoregulatory hypothesis" of food intake...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29526023/contribution-of-dynorphin-and-orexin-neuropeptide-systems-to-the-motivational-effects-of-alcohol
#5
Rachel I Anderson, David E Moorman, Howard C Becker
Understanding the neural systems that drive alcohol motivation and are disrupted in alcohol use disorders is of critical importance in developing novel treatments. The dynorphin and orexin/hypocretin neuropeptide systems are particularly relevant with respect to alcohol use and misuse. Both systems are strongly associated with alcohol-seeking behaviors, particularly in cases of high levels of alcohol use as seen in dependence. Furthermore, both systems also play a role in stress and anxiety, indicating that disruption of these systems may underlie long-term homeostatic dysregulation seen in alcohol use disorders...
March 11, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29508004/the-hypocretin-orexin-system-as-a-target-for-excessive-motivation-in-alcohol-use-disorders
#6
REVIEW
David E Moorman
The hypocretin/orexin (ORX) system has been repeatedly demonstrated to regulate motivation for drugs of abuse, including alcohol. In particular, ORX seems to be critically involved in highly motivated behaviors, as is observed in high-seeking individuals in a population, in the seeking of highly palatable substances, and in models of dependence. It seems logical that this system could be considered as a potential target for treatment for addiction, particularly alcohol addiction, as ORX pharmacological manipulations significantly reduce drinking...
June 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29479060/a-gabaergic-cell-type-in-the-lateral-habenula-links-hypothalamic-homeostatic-and-midbrain-motivation-circuits-with-sex-steroid-signaling
#7
Limei Zhang, Vito S Hernández, Jerome D Swinny, Anil K Verma, Torsten Giesecke, Andrew C Emery, Kerim Mutig, Luis M Garcia-Segura, Lee E Eiden
The lateral habenula (LHb) has a key role in integrating a variety of neural circuits associated with reward and aversive behaviors. There is limited information about how the different cell types and neuronal circuits within the LHb coordinate physiological and motivational states. Here, we report a cell type in the medial division of the LHb (LHbM) in male rats that is distinguished by: (1) a molecular signature for GABAergic neurotransmission (Slc32a1/VGAT) and estrogen receptor (Esr1/ERα) expression, at both mRNA and protein levels, as well as the mRNA for vesicular glutamate transporter Slc17a6/VGLUT2, which we term the GABAergic estrogen-receptive neuron (GERN); (2) its axonal projection patterns, identified by in vivo juxtacellular labeling, to both local LHb and to midbrain modulatory systems; and (3) its somatic expression of receptors for vasopressin, serotonin and dopamine, and mRNA for orexin receptor 2...
February 26, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29289556/chronopathophysiological-implications-of-orexin-in-sleep-disturbances-and-lifestyle-related-disorders
#8
REVIEW
Hiroshi Tsuneki, Tsutomu Wada, Toshiyasu Sasaoka
Sleep, a mysterious behavior, has recently been recognized as a crucial factor for health and longevity. The daily sleep/wake cycle provides the basis of biorhythms controlling whole-body homeostasis and homeodynamics; therefore, disruption of sleep causes several physical and psychological disorders, including cardiovascular disease, obesity, diabetes, cancer, anxiety, depression, and cognitive dysfunction. However, the mechanism linking sleep disturbances and sleep-related disorders remains unknown. Orexin (also known as hypocretin) is a neuropeptide produced in the hypothalamus...
December 29, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29129052/synthesis-and-evaluation-of-orexin-1-receptor-antagonists-with-improved-solubility-and-cns-permeability
#9
David A Perrey, Ann M Decker, Yanan Zhang
Orexins are hypothalamic neuropeptides playing important roles in many functions including the motivation of addictive behaviors. Blockade of the orexin-1 receptor has been suggested as a potential strategy for the treatment of drug addiction. We have previously reported OX1 receptor antagonists based on the tetrahydroisoquinoline scaffold with excellent OX1 potency and selectivity; however, these compounds had high lipophilicity (clogP > 5) and low to moderate solubility. In an effort to improve their properties, we have designed and synthesized a series of analogues where the 7-position substituents known to favor OX1 potency and selectivity were retained, and groups of different nature were introduced at the 1-position where substitution was generally tolerated as demonstrated in previous studies...
November 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29089444/presynaptic-regulation-of-leptin-in-a-defined-lateral-hypothalamus-ventral-tegmental-area-neurocircuitry-depends-on-energy-state
#10
Jing-Jing Liu, Nicholas T Bello, Zhiping P Pang
Synaptic transmission controls brain activity and behaviors, including food intake. Leptin, an adipocyte-derived hormone, acts on neurons located in the lateral hypothalamic area (LHA) to maintain energy homeostasis and regulate food intake behavior. The specific synaptic mechanisms, cell types, and neural projections mediating this effect remain unclear. In male mice, using pathway-specific retrograde tracing, whole-cell patch-clamp recordings and post hoc cell type identification, we found that leptin reduces excitatory synaptic strength onto both melanin-concentrating hormone- and orexin-expressing neurons projecting from the LHA to the ventral tegmental area (VTA), which may affect dopamine signaling and motivation for feeding...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29073109/opioid-and-orexin-hedonic-hotspots-in-rat-orbitofrontal-cortex-and-insula
#11
Daniel C Castro, Kent C Berridge
Hedonic hotspots are brain sites where particular neurochemical stimulations causally amplify the hedonic impact of sensory rewards, such as "liking" for sweetness. Here, we report the mapping of two hedonic hotspots in cortex, where mu opioid or orexin stimulations enhance the hedonic impact of sucrose taste. One hedonic hotspot was found in anterior orbitofrontal cortex (OFC), and another was found in posterior insula. A suppressive hedonic coldspot was also found in the form of an intervening strip stretching from the posterior OFC through the anterior and middle insula, bracketed by the two cortical hotspots...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29052613/dynorphin-counteracts-orexin-in-the-paraventricular-nucleus-of-the-thalamus-cellular-and-behavioral-evidence
#12
Alessandra Matzeu, Marsida Kallupi, Olivier George, Paul Schweitzer, Rémi Martin-Fardon
The orexin (Orx) system plays a critical role in drug addiction and reward-related behaviors. The dynorphin (Dyn) system promotes depressive-like behavior and plays a key role in the aversive effects of stress. Orx and Dyn are co-released and have opposing functions in reward and motivation in the ventral tegmental area (VTA). Previous studies suggested that OrxA transmission in the posterior paraventricular nucleus of the thalamus (pPVT) participates in cocaine-seeking behavior. This study determined whether Orx and Dyn interact in the pPVT...
April 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28858406/chemogenetic-activation-of-the-lateral-hypothalamus-reverses-early-life-stress-induced-deficits-in-motivational-drive
#13
Erin J Campbell, Caitlin S Mitchell, Cameron D Adams, Jiann Wei Yeoh, Deborah M Hodgson, Brett A Graham, Christopher V Dayas
Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions including mood disorders. One well-characterized antecedent to the development of mood disorders is exposure to early life stress (ELS). A key brain substrate controlling motivated behaviour is the lateral hypothalamus (LH). Here, we examined the effect of ELS on LH activation and the motivation to self-administer sucrose. We tested whether chemogenetic activation of LH circuits could modify sucrose responding in ELS rats and examined the impact on LH cell populations...
October 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28741623/effects-of-suvorexant-a-dual-orexin-hypocretin-receptor-antagonist-on-impulsive-behavior-associated-with-cocaine
#14
Taylor A Gentile, Steven J Simmons, Mia N Watson, Krista L Connelly, Eugen Brailoiu, Yanan Zhang, John W Muschamp
Hypothalamic hypocretin (orexin) peptides mediate arousal, attention, and reward processing. Fibers containing orexins project to brain structures that govern motivated behavior, including the ventral tegmental area (VTA). A number of psychiatric conditions, including attention deficit hyperactivity disorder (ADHD) and substance use disorders, are characterized by deficits in impulse control, however the relationship between orexin and impulsive behavior is incompletely characterized. The effects of systemic or centrally administered orexin receptor (OXR) antagonists on measures of impulsive-like behavior in rats were evaluated using the five-choice serial reaction time task (5-CSRTT) and delay discounting procedures...
April 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28705440/inhibition-of-trkb-at-the-nucleus-accumbens-using-ana-12-regulates-basal-and-stress-induced-orexin-a-expression-within-the-mesolimbic-system-and-affects-anxiety-sociability-and-motivation
#15
Idu Azogu, Helene Plamondon
Repeated stress exposure can lead to the development of anxiety and mood disorders. An emerging biological substrate of depression and associated pathology is the nucleus accumbens (NAc), which through interactions with limbic, cognitive and motor circuits can regulate a variety of stress responses. Within these circuits, orexin neurons are involved in arousal and stress adaptability, effects proposed mediated via brain-derived neurotrophic factor signaling. This study tested the hypotheses that 1) repeated exposure to heterotypic stress alters social ability and preference and passive avoidant behaviors, 2) TrkB receptors at the NAc shell regulates stress-induced behavioral responses and orexin expression within the mesocorticolimbic system...
October 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28663114/palatable-food-self-administration-and-reinstatement-are-not-affected-by-dual-orexin-receptor-antagonism
#16
Shaun Yon-Seng Khoo, Kelly J Clemens, Gavan P McNally
The orexins are widely regarded potential therapeutic targets for a range of disorders of appetitive motivation, including obesity. The motivational activator theory, the first coherent account of the orexin system's role in appetitive motivation, predicts that orexin release motivates appetitive behaviour when the reinforcer is highly salient, available under a high unit-cost or when reward seeking is cue-driven. The present study tested the effect of intracerebroventricular (i.c.v.) administration of the highly potent and commercially available dual orexin receptor antagonist, TCS 1102, on self-administration and reinstatement of palatable food seeking in hungry and sated rats...
June 27, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28631980/orexin-research-patent-news-from-2016
#17
REVIEW
Christoph Boss, Catherine Roch
The orexin system consists of two G-protein-coupled receptors, orexin 1 and orexin 2 and two endogenous ligands, orexin A and orexin B . It is evolutionarily highly conserved. It is involved in the promotion of wakefulness as well as in anxiety and addictive disorders. In addition, its activation via the Ox1 receptor triggers apoptosis in several cancer cell lines. Dual orexin receptor antagonists are successfully used to treat primary insomnia. The major open questions are now related to the clinical validation of Ox1 selective antagonists...
October 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28630298/hypocretin-orexin-is-critical-in-sustaining-theta-gamma-rich-waking-behaviors-that-drive-sleep-need
#18
Anne Vassalli, Paul Franken
Hcrt gene inactivation in mice leads to behavioral state instability, abnormal transitions to paradoxical sleep, and cataplexy, hallmarks of narcolepsy. Sleep homeostasis is, however, considered unimpaired in patients and narcoleptic mice. We find that whereas Hcrt(ko/ko) mice respond to 6-h sleep deprivation (SD) with a slow-wave sleep (SWS) EEG δ (1.0 to 4.0 Hz) power rebound like WT littermates, spontaneous waking fails to induce a δ power reflecting prior waking duration. This correlates with impaired θ (6...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28419646/suvorexant-an-orexin-hypocretin-receptor-antagonist-attenuates-motivational-and-hedonic-properties-of-cocaine
#19
Taylor A Gentile, Steven J Simmons, David J Barker, Jessica K Shaw, Rodrigo A España, John W Muschamp
Orexins ('hypocretins') are peptides produced by neurons of the hypothalamus that project to structures implicated in reward and emotion processing. Converging evidence demonstrates functional roles of orexin signaling in arousal, sleep/wakefulness and motivated behaviors for natural and drug rewards. Suvorexant, a dual orexin receptor antagonist, recently received approval from the US Food and Drug Administration to treat insomnia. In Experiment 1, rats self-administered cocaine under a progressive-ratio schedule of reinforcement and the effects of suvorexant on motivation to self-administer cocaine were measured...
January 2018: Addiction Biology
https://www.readbyqxmd.com/read/28303403/hypocretin-orexin-and-plastic-adaptations-associated-with-drug-abuse
#20
Corey Baimel, Stephanie L Borgland
Dopamine neurons in the ventral tegmental area (VTA) are a critical part of the neural circuits that underlie reward learning and motivation. Dopamine neurons send dense projections throughout the brain and recent observations suggest that both the intrinsic properties and the functional output of dopamine neurons are dependent on projection target and are subject to neuromodulatory influences. Lateral hypothalamic hypocretin (also termed orexin) neurons project to the VTA and contain both hypocretin and dynorphin peptides in the same dense core vesicles suggesting they may be co-released...
2017: Current Topics in Behavioral Neurosciences
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