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Dynorphin

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https://www.readbyqxmd.com/read/28802836/neocortical-prodynorphin-expression-is-transiently-increased-with-learning-implications-for-time-and-learning-dependent-neocortical-kappa-opioid-receptor-activation
#1
Ryan Loh, Sean Collins, Roberto Galvez
There are several lines of evidence that indicate a prominent role for the opioid system in the acquisition and consolidation of learned associations. Specifically, kappa opioid receptor (KOR) modulation has been demonstrated to alter various behavioral tasks including whisker trace eyeblink conditioning (WTEB). WTEB is an associative conditioning paradigm in which a neutral conditioned stimulus (CS; Whisker stimulation) is paired following a short stimulus free trace interval with a salient unconditioned stimulus that elicits a blink response (US; Eye shock)...
August 9, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28800500/sb223412-a-neurokinin-3-receptor-selective-antagonist-suppresses-testosterone-secretion-in-male-guinea-pigs
#2
Sho Nakamura, Yoshiko Ito, Koki Yamamoto, Chudai Takahashi, Mingdao Dai, Miyu Tanahashi, Yoshihisa Uenoyama, Hiroko Tsukamura, Shinya Oishi, Kei-Ichiro Maeda, Fuko Matsuda
Guinea pigs are important zoo animals and have been recommended for animal-assisted activities or therapy, however there are problems concerning testosterone inducing aggressive or sexual behaviors in male guinea pigs. Testicular testosterone secretion is regulated by pulsatile gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH) release in mammals. The mechanism generating GnRH/LH pulses is thought to be governed by kisspeptin neurons, which coexpress neurokinin B (NKB) and dynorphin A (Dyn), in the arcuate nucleus (ARC)...
July 31, 2017: Theriogenology
https://www.readbyqxmd.com/read/28726252/central-amygdala-relaxin-3-rxfp3-signalling-modulates-alcohol-seeking-in-rats
#3
Leigh C Walker, Hanna E Kastman, Elena Krstew, Andrew L Gundlach, Andrew J Lawrence
BACKGROUND AND PURPOSE: Alcohol use disorders are a leading cause of preventable deaths worldwide and stress is a major trigger of relapse. The neuropeptide relaxin-3 and its cognate receptor, relaxin family peptide receptor 3 (RXFP3), modulate stress-induced relapse to alcohol seeking in rats and while the bed nucleus of the stria terminalis has been implicated in this regard, the central nucleus of the amygdala (CeA) also receives a relaxin-3 innervation and CeA neurons densely express RXFP3 mRNA...
July 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28722336/evidence-for-the-modulation-of-nociception-in-mice-by-central-mast-cells
#4
C L Kissel, K J Kovács, A A Larson
BACKGROUND: Hyperalgesia that develops following nerve ligation corresponds temporally and in magnitude with the number of thalamic mast cells located contralateral to the ligature. We tested the possibility that mast cells modulate nociception centrally, similar to their role in the periphery. METHODS: We examined the central effect of two hyperalgesic compounds that induce mast cell degranulation and of stabilized mast cells using cromolyn. RESULTS: Thermal hyperalgesia (tail flick) induced by nerve growth factor (NGF, a neurotrophic compound) and mechanical hyperalgesia (von Frey) induced by dynorphin A (1-17) (opioid compound) each correlated with the per cent of thalamic mast cells that were degranulated...
July 19, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28664358/oxytocin-intranasal-administration-affects-neural-networks-upstream-of-gnrh-neurons
#5
Mohammad Saied Salehi, Homayoun Khazali, Fariba Mahmoudi, Mahyar Janahmadi
The last decade has witnessed a surge in studies on the clinical applications of intranasal oxytocin as a method of enhancing social interaction. However, the molecular and cellular mechanisms underlying its function are not completely understood. Since oxytocin is involved in the regulation of hypothalamic-pituitary-gonadal axis by affecting the gonadotropin-releasing hormone (GNRH) system, the present study addressed whether intranasal application of oxytocin has a role in affecting GNRH expression in the male rat hypothalamus...
August 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28653356/arcuate-nucleus-homeostatic-systems-reflect-blood-leptin-concentration-but-not-feeding-behaviour-during-scheduled-feeding-on-a-high-fat-diet-in-mice
#6
T Bake, J Baron, J S Duncan, D G A Morgan, J G Mercer
Hypothalamic homeostatic and forebrain reward-related genes were examined in the context of scheduled meal feeding without caloric restriction in C57BL/6 mice. Mice fed ad libitum but allowed access to a palatable high fat diet for 2 h a day rapidly adapted their feeding behaviour and consumed approximately 80% of their daily caloric intake during this 2 h scheduled feed. Gene expression levels were examined during either the first or second hour of scheduled feeding vs. 24 h ad libitum feeding on the same high fat diet...
June 27, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28649993/kappa-opioid-receptor-activation-in-dopamine-neurons-disrupts-behavioral-inhibition
#7
Antony D Abraham, Harrison M Fontaine, Allisa J Song, Mackenzie M Andrews, Madison A Baird, Brigitte L Kieffer, Benjamin B Land, Charles Chavkin
The dynorphin/kappa opioid receptor (KOR) system has been previously implicated in the regulation of cognition, but the neural circuitry and molecular mechanisms underlying KOR-mediated cognitive disruption are unknown. Here, we used an operational test of cognition involving timing and behavioral inhibition and found that systemic KOR activation impairs performance of male and female C57BL/6 mice in the differential reinforcement of low response rates (DRL) task. Systemic KOR antagonism also blocked stress-induced disruptions of DRL performance...
June 26, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28630099/kndy-neurone-activation-prior-to-the-lh-surge-of-the-ewe-is-disrupted-by-lps
#8
Chrysanthi Fergani, Jean Routly, David Jones, Lucy Pickavance, Robert Frank Smith, Hilary Dobson
In the ewe, steroid hormones act on the hypothalamic arcuate nucleus (ARC) to initiate the GnRH/LH surge. Within the ARC, steroid signal transduction may be mediated by dopamine, β-endorphin or neuropeptide Y (NPY) expressing cells, as well as those co-localising kisspeptin, neurokinin B (NKB), and dynorphin (termed KNDy). We investigated the time during the follicular phase when these cells become activated (i.e., co-localise c-Fos) relative to the timing of the LH surge onset and may, therefore, be involved in the surge generating mechanism...
June 19, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28589966/role-of-%C3%AE%C2%BA-opioid-receptors-in-the-bed-nucleus-of-stria-terminalis-in-reinstatement-of-alcohol-seeking
#9
A D Lê, Douglas Funk, Kathleen Coen, Sahar Tamadon, Yavin Shaham
κ-Opioid receptors (KORs) and their endogenous ligand dynorphin are involved in stress-induced alcohol seeking but the mechanisms involved are largely unknown. We previously showed that systemic injections of the KOR agonist U50,488, which induce stress-like aversive states, reinstate alcohol seeking after extinction of the alcohol-reinforced responding. Here, we used the neuronal activity marker Fos and site-specific injections of the KOR antagonist nor-BNI and U50,488 to study brain mechanisms of U50,488-induced reinstatement of alcohol seeking...
June 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28475285/evidence-of-involvement-of-neurone-glia-neurone-neurone-communications-via-gap-junctions-in-synchronised-activity-of-kndy-neurones
#10
K Ikegami, S Minabe, N Ieda, T Goto, A Sugimoto, S Nakamura, N Inoue, S Oishi, A D Maturana, M Sanbo, M Hirabayashi, K-I Maeda, H Tsukamura, Y Uenoyama
Pulsatile secretion of gonadotrophin-releasing hormone (GnRH)/luteinising hormone is indispensable for the onset of puberty and reproductive activities at adulthood in mammalian species. A cohort of neurones expressing three neuropeptides, namely kisspeptin, encoded by the Kiss1 gene, neurokinin B (NKB) and dynorphin A, localised in the hypothalamic arcuate nucleus (ARC), so-called KNDy neurones, comprises a putative intrinsic source of the GnRH pulse generator. Synchronous activity among KNDy neurones is considered to be required for pulsatile GnRH secretion...
June 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28464209/alanine-scan-of-the-opioid-peptide-dynorphin-b-amide
#11
Anand A Joshi, Thomas F Murray, Jane V Aldrich
To date structure-activity relationship (SAR) studies of the dynorphins (Dyn), endogenous peptides for kappa opioid receptors (KOR), have focused almost exclusively on Dyn A with minimal studies on Dyn B. While both Dyn A and Dyn B have identical N-terminal sequences, their C-terminal sequences differ which could result in differences in pharmacological activity. We performed an alanine scan of the non-glycine residues up through residue 11 of Dyn B amide to explore the role of these side chains in the activity of Dyn B...
May 2, 2017: Biopolymers
https://www.readbyqxmd.com/read/28449351/long-term-plasticity-of-corticostriatal-synapses-is-modulated-by-pathway-specific-co-release-of-opioids-through-%C3%AE%C2%BA-opioid-receptors
#12
Sarah L Hawes, Armando G Salinas, David M Lovinger, Kim T Blackwell
KEY POINTS: Both endogenous opioids and opiate drugs of abuse modulate learning of habitual and goal-directed actions, and can also modify long-term plasticity of corticostriatal synapses. Striatal projection neurons of the direct pathway co-release the opioid neuropeptide dynorphin which can inhibit dopamine release via κ-opioid receptors. Theta-burst stimulation of corticostriatal fibres produces long-term potentiation (LTP) in striatal projection neurons when measured using whole-cell patch recording...
August 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28444173/tac1-signaling-is-required-for-sexual-maturation-and-responsiveness-of-gnrh-neurons-to-kisspeptin-in-the-male-mouse
#13
Caroline A Maguire, Yong Bhum Song, Min Wu, Silvia León, Rona S Carroll, Meenakshi Alreja, Ursula B Kaiser, Víctor M Navarro
The tachykinins substance P (SP) and neurokinin A (NKA) (Tac1) have emerged as novel regulators of kisspeptin/GnRH release. Recently, we documented that SP modulates reproductive function in the female mouse. Here, we extended this characterization to the male mouse. Tac1-/- male mice showed delayed puberty onset. They also presented significantly decreased expression levels of Pdyn (dynorphin) and Nos1 (nitric oxide synthase) in the mediobasal hypothalamus and elevated Gnrh1 levels. Unexpectedly, the response of Tac1-/- mice to central kisspeptin or senktide (neurokinin B receptor -NK3R- agonist) administration was significantly decreased compared with controls, despite the preserved ability of GnRH neurons to stimulate LH release as demonstrated by central NMDA administration, suggesting a deficit at the GnRH neuron level...
April 21, 2017: Endocrinology
https://www.readbyqxmd.com/read/28442370/modulation-of-drug-choice-by-extended-drug-access-and-withdrawal-in-rhesus-monkeys-implications-for-negative-reinforcement-as-a-driver-of-addiction-and-target-for-medications-development
#14
REVIEW
S Stevens Negus, Matthew L Banks
Chronic drug exposure is hypothesized to recruit negative reinforcement processes that increase the magnitude and alter the mechanisms of drug reinforcement. Candidate substrates of negative reinforcement include increased signaling via stress-related neurotransmitters such as corticotropin releasing factor (CRF, acting at CRF receptors) or dynorphin (acting at kappa opioid receptors) and/or decreased signaling via reward-related neurotransmitters such as dopamine. Determinants of drug reinforcement can be examined with choice procedures, in which subjects choose between a drug of interest (e...
April 22, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28431971/influence-of-stress-associated-with-chronic-alcohol-exposure-on-drinking
#15
REVIEW
Howard C Becker
Stress is commonly regarded as an important trigger for relapse and a significant factor that promotes increased motivation to drink in some individuals. However, the relationship between stress and alcohol is complex, likely changing in form during the transition from early moderated alcohol use to more heavy uncontrolled alcohol intake. A growing body of evidence indicates that prolonged excessive alcohol consumption serves as a potent stressor, producing persistent dysregulation of brain reward and stress systems beyond normal homeostatic limits...
August 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28425121/role-of-the-dynorphin-kappa-opioid-receptor-system-in-the-motivational-effects-of-ethanol
#16
REVIEW
Rachel I Anderson, Howard C Becker
Evidence has demonstrated that dynorphin (DYN) and the kappa opioid receptor (KOR) system contribute to various psychiatric disorders, including anxiety, depression, and addiction. More recently, this endogenous opioid system has received increased attention as a potential therapeutic target for treating alcohol use disorders. In this review, we provide an overview and synthesis of preclinical studies examining the influence of alcohol (ethanol [EtOH]) exposure on DYN/KOR expression and function, as well as studies examining the effects of DYN/KOR manipulation on EtOH's rewarding and aversive properties...
August 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28376659/kappa-opioid-receptor-antagonists-a-possible-new-class-of-therapeutics-for-migraine-prevention
#17
Jennifer Y Xie, Milena De Felice, Caroline M Kopruszinski, Nathan Eyde, Justin LaVigne, Bethany Remeniuk, Pablo Hernandez, Xu Yue, Naomi Goshima, Michael Ossipov, Tamara King, John M Streicher, Edita Navratilova, David Dodick, Hugh Rosen, Ed Roberts, Frank Porreca
Background Stress is the most commonly reported migraine trigger. Dynorphin, an endogenous opioid peptide acting preferentially at kappa opioid receptors (KORs), is a key mediator of stress responses. The aim of this study was to use an injury-free rat model of functional cephalic pain with features of migraine and medication overuse headache (MOH) to test the possible preventive benefit of KOR blockade on stress-induced cephalic pain. Methods Following sumatriptan priming to model MOH, rats were hyper-responsive to environmental stress, demonstrating delayed cephalic and extracephalic allodynia and increased levels of CGRP in the jugular blood, consistent with commonly observed clinical outcomes during migraine...
July 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28363796/structure-constrained-endomorphin-analogs-display-differential-antinociceptive-mechanisms-in-mice-after-spinal-administration
#18
Yuan Wang, Jingjing Zhou, Xin Liu, Long Zhao, Zhaojuan Wang, Xianghui Zhang, Kezhou Wang, Linqing Wang, Rui Wang
We previously reported a series of novel endomorphin analogs with unnatural amino acid modifications. These analogs display good binding affinity and functional activity toward the μ opioid receptor (MOP). In the present study, we further investigated the spinal antinociceptive activity of these compounds. The analogs were potent in several nociceptive models. Opioid antagonists and antibodies against several endogenous opioid peptides were used to determine the mechanisms of action of these peptides. Intrathecal pretreatment with naloxone and β-funaltrexamine (β-FNA) effectively inhibited analog-induced analgesia, demonstrating that activity of the analogs is regulated primarily through MOP...
May 2017: Peptides
https://www.readbyqxmd.com/read/28350441/chemical-probes-unravel-an-antimicrobial-defense-response-triggered-by-binding-of-the-human-opioid-dynorphin-to-a-bacterial-sensor-kinase
#19
Megan H Wright, Christian Fetzer, Stephan A Sieber
Host-microbe communication via small molecule signals is important for both symbiotic and pathogenic relationships, but is often poorly understood at the molecular level. Under conditions of host stress, levels of the human opioid peptide dynorphin are elevated, triggering virulence in the opportunistic pathogenic bacterium Pseudomonas aeruginosa via an unknown pathway. Here we apply a multilayered chemical biology strategy to unravel the mode of action of this putative interkingdom signal. We designed and applied dynorphin-inspired photoaffinity probes to reveal the protein targets of the peptide in live bacteria via chemical proteomics...
April 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28336495/genetic-variation-and-epigenetic-modification-of-the-prodynorphin-gene-in-peripheral-blood-cells-in-alcoholism
#20
Claudio D'Addario, Klementy Shchetynsky, Mariangela Pucci, Carlo Cifani, Agneta Gunnar, Vladana Vukojević, Leonid Padyukov, Lars Terenius
Dynorphins are critically involved in the development, maintenance and relapse of alcoholism. Alcohol-induced changes in the prodynorphin gene expression may be influenced by both gene polymorphisms and epigenetic modifications. The present study of human alcoholics aims to evaluate DNA methylation patterns in the prodynorphin gene (PDYN) promoter and to identify single nucleotide polymorphisms (SNPs) associated with alcohol dependence and with altered DNA methylation. Genomic DNA was isolated from peripheral blood cells of alcoholics and healthy controls, and DNA methylation was studied in the PDYN promoter by bisulfite pyrosequencing...
March 21, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
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