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https://www.readbyqxmd.com/read/27916688/effects-of-repeated-treatment-with-a-delta-opioid-receptor-agonist-knt-127-on-hyperemotionality-in-olfactory-bulbectomized-rats
#1
Leo Gotoh, Akiyoshi Saitoh, Misa Yamada, Hideaki Fujii, Hiroshi Nagase, Mitsuhiko Yamada
We previously demonstrated that a single treatment of a non-peptidic delta opioid receptor agonist, KNT-127, has an antidepressant-like effect in rodents in the forced swim test. Here we evaluated the effect of repeated administration of the potential antidepressant KNT-127 in an olfactory-bulbectomized (OBX) rat model. Male Wistar rats (8-12 weeks old) underwent olfactory bulbectomy. From 14days after surgery each was weighed and administered either KNT-127 (3mgkg(-1)/day), the selective serotonin reuptake inhibitor (SSRI) fluoxetine (10mgkg(-1)/day), or vehicle, daily for 14 days...
December 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27913257/prodynorphin-and-kappa-opioid-receptor-mrna-expression-in-the-brain-relates-to-social-status-and-behavior-in-male-european-starlings
#2
Lauren V Riters, Melissa A Cordes, Sharon A Stevenson
Numerous animal species display behavioral changes in response to changes in social status or territory possession. For example, in male European starlings only males that acquire nesting sites display high rates of sexual and agonistic behavior. Past studies show that mu and delta opioid receptors regulate behaviors associated with social ascension or defeat. Opioids also act at kappa receptors, with dynorphin binding with the highest affinity; however, the role of these opioids in social behavior has not been well studied...
November 29, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27862489/amygdala-mu-opioid-receptors-mediate-the-motivating-influence-of-cue-triggered-reward-expectations
#3
Nina T Lichtenberg, Kate M Wassum
Environmental reward-predictive stimuli can retrieve from memory a specific reward expectation that allows them to motivate action and guide choice. This process requires the basolateral amygdala (BLA), but little is known about the signaling systems necessary within this structure. Here we examined the role of the neuromodulatory opioid receptor system in the BLA in such cue-directed action using the outcome-specific Pavlovian-to-instrumental transfer (PIT) test in rats. Inactivation of BLA mu-, but not delta-opioid receptors was found to dose-dependently attenuate the ability of a reward-predictive cue to selectively invigorate the performance of actions directed at the same unique predicted reward (i...
November 12, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27852962/anatomy-and-immunochemical-characterization-of-the-non-arterial-peptidergic-diffuse-dural-innervation-of-the-rat-and-rhesus-monkey-implications-for-functional-regulation-and-treatment-in-migraine
#4
Frank L Rice, Jennifer Y Xie, Phillip J Albrecht, Emily Acker, Justin Bourgeois, Edita Navratilova, David W Dodick, Frank Porreca
OBJECTIVE: The interplay between neuronal innervation and other cell types underlies the physiological functions of the dura mater and contributes to pathophysiological conditions such as migraine. We characterized the extensive, but understudied, non-arterial diffuse dural innervation (DDI) of the rat and Rhesus monkey. METHODS: We used a comprehensive integrated multi-molecular immunofluorescence labeling strategy to extensively profile the rat DDI and to a lesser extent that of the Rhesus monkey...
November 16, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27849613/endogenous-central-amygdala-mu-opioid-receptor-signaling-promotes-sodium-appetite-in-mice
#5
Craig M Smith, Lesley L Walker, Tanawan Leeboonngam, Michael J McKinley, Derek A Denton, Andrew J Lawrence
Due to the importance of dietary sodium and its paucity within many inland environments, terrestrial animals have evolved an instinctive sodium appetite that is commensurate with sodium deficiency. Despite a well-established role for central opioid signaling in sodium appetite, the endogenous influence of specific opioid receptor subtypes within distinct brain regions remains to be elucidated. Using selective pharmacological antagonists of opioid receptor subtypes, we reveal that endogenous mu-opioid receptor (MOR) signaling strongly drives sodium appetite in sodium-depleted mice, whereas a role for kappa (KOR) and delta (DOR) opioid receptor signaling was not detected, at least in sodium-depleted mice...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27842940/nalmefene-for-the-management-of-alcohol-dependence-review-on-its-pharmacology-mechanism-of-action-and-meta-analysis-on-its-clinical-efficacy
#6
Karl Mann, Lars Torup, Per Sørensen, Antoni Gual, Robert Swift, Brendan Walker, Wim van den Brink
Nalmefene, a mu- and delta-opioid receptor (MOR, DOR) antagonist and a partial kappa-opioid receptor (KOR) agonist, is approved in the European Union and other countries for the reduction of alcohol consumption in alcohol dependent patients with a high drinking risk level according to WHO ("target population"). This review presents an overview of nalmefene׳s pharmacology, its mechanisms of action and a meta-analysis on its efficacy in reducing alcohol consumption. The review was based on a systematic search of the literature...
December 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27787711/delta-opioid-receptor-dor-ligands-and-pharmacology-development-of-indolo-and-quinolinomorphinan-derivatives-based-on-the-message-address-concept
#7
Akiyoshi Saitoh, Hiroshi Nagase
The pharmacology of the delta opioid receptor (DOR) has lagged, mainly due to the lack of an agonist with high potency and selectivity in vivo. The DOR is now receiving increasing attention, and there has been progress in the synthesis of better novel ligands. The discovery of a selective receptor DOR antagonist, naltrindole (NTI), stimulated the design and synthesis of (±)TAN-67, which was designed based on the message-address concept and the accessory site theory. Intensive studies using (±)TAN-67 determined the DOR-mediated various pharmacological effects, such as antinociceptive effects for painful diabetic neuropathy and cardiovascular protective effects...
October 28, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27764759/6-methoxyflavanone-attenuates-mechanical-allodynia-and-vulvodynia-in-the-streptozotocin-induced-diabetic-neuropathic-pain
#8
Shehla Akbar, Fazal Subhan, Nasiara Karim, Muhammad Shahid, Nisar Ahmad, Gowhar Ali, Wajahat Mahmood, Khwaja Fawad
BACKGROUND: Diabetic neuropathy is the most prevalent, persistent and debilitating complication of diabetes mellitus often coupled with vulvodynia that may present as an isolated symptom or as a part of constellation of other neuropathic abnormalities. OBJECTIVE: Flavonoids have selective affinity for GABA receptors and 6-methoxyflavanone (6-MeOF) is a positive allosteric modulator of GABA responses at human recombinant GABAA receptors. GABAergic and opioidergic system inhibition have been shown to facilitate neuropathic pain...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27762555/synthesis-of-gly-%C3%AE-z-cf-ch-phe-a-fluoroalkene-dipeptide-isostere-and-its-incorporation-into-a-leu-enkephalin-peptidomimetic
#9
Jean-Francois Nadon, Kristina Rochon, Sébastien Grastilleur, Guillaume Langlois, Thi Thanh Hà Dao, Véronique Blais, Brigitte Guérin, Louis Gendron, Yves L Dory
A new Leu-enkephalin peptidomimetic designed to explore the hydrogen bond acceptor ability of the third peptide bond has been prepared and studied. This new analog is produced by replacing the third amide of Leu-enkephalin with a fluoroalkene. An efficient and innovative synthesis of the corresponding dipeptide surrogate Fmoc-Gly-Ψ[(Z)CF=CH]-Phe-OH is described. The key step involves the alkylation of a tin dienolate from the less hindered face of its chiral sulfonamide auxiliary derived from camphor. Once its synthesis was complete, its incorporation into the peptidomimetic sequence was achieved on a solid support with chlorotrityl resin and following the Fmoc strategy...
October 20, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27749013/high-motivation-for-exercise-is-associated-with-altered-chromatin-regulators-of-monoamine-receptor-gene-expression-in-the-striatum-of-selectively-bred-mice
#10
Michael Saul, Petra Majdak, Samuel Perez, Matthew Reilly, Theodore Garland, Justin S Rhodes
Though exercise is critical for health, many lack the motivation to exercise, and it is unclear how motivation might be increased. To uncover the molecular underpinnings of increased motivation for exercise, we analyzed the transcriptome of the striatum in four mouse lines selectively bred for high voluntary wheel running and four non-selected control lines. The striatum was dissected and RNA was extracted and sequenced from four individuals of each line. We found multiple genes and gene systems with strong relationships to both selection and running history over the previous 6 days...
October 17, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27748566/mu-and-delta-opioid-receptor-knockout-mice-show-increased-colonic-sensitivity
#11
D Reiss, R A Ceredig, T Secher, J Boué, F Barreau, G Dietrich, C Gavériaux-Ruff
BACKGROUND: Opiates act through opioid receptors to diminish pain. Here, we investigated whether mu (MOR) and delta (DOR) receptor endogenous activity assessed in the whole mouse body or in particular at peripheral receptors on primary nociceptive neurons, control colonic pain. METHODS: We compared global MOR and DOR receptor knockout (KO) mice, mice with a conditional deletion of MOR and DOR in Nav1.8-positive nociceptive primary afferent neurons (cKO), and control floxed mice of both genders for visceral sensitivity...
October 17, 2016: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/27736284/continuous-perioperative-sublingual-buprenorphine
#12
Marcelina Jasmine Silva, Andrea Rubinstein
Buprenorphine, a semisynthetic thebaine derivative, is a unique opioid, as it has activity at multiple receptors, including mu (partial agonist), kappa (antagonist), OLR-1 (agonist), and delta (antagonist). Because buprenorphine's pharmacology is relatively complex, misconceptions about its actions are common. Most other opioids act solely or predominately as full mu receptor agonists. Common practice at many institutions calls for the cessation of regular buprenorphine use 48-72 hours prior to surgery. This practice is based on three foundational theories that have come from scant data about the properties of buprenorphine: (1) that buprenorphine is only a partial mu agonist and therefore is not a potent analgesic; (2) because buprenorphine has a ceiling effect on respiratory depression, it also has a ceiling effect on analgesia; and (3) that buprenorphine acts as a "blockade" to the analgesic effects of other opiates when coadministered due to its strong binding affinity...
October 13, 2016: Journal of Pain & Palliative Care Pharmacotherapy
https://www.readbyqxmd.com/read/27734456/-opioidergic-postconditioning-of-heart-muscle-during-ischemia-reperfusion-injury
#13
Marcin Kunecki, Wojciech Płazak, Tomasz Roleder, Jolanta Biernat, Tomasz Oleksy, Piotr Podolec, Krzysztof Stanisław Gołba
BACKGROUND: Ischemic preconditioning (IPC) and postconditioning (POC) are the novel strategies of attaining cardioprotection against ischemia/reperfusion (I/R) injury. Previous studies suggested the role of opioid pathway, however the class of opioid receptors responsible for this effect in humans remains unknown. The aim of the study was to assess the influence of opioids on simulated I/R injury outcomes in the human myocardium. METHODS: Trabeculae of the human right atrium were electrically driven in organ bath and subjected to simulated I/R injury...
October 13, 2016: Cardiology Journal
https://www.readbyqxmd.com/read/27725218/opioid-subtype-and-cell-type-dependent-regulation-of-inhibitory-synaptic-transmission-in-the-rat-insular-cortex
#14
Eiko Yokota, Yuko Koyanagi, Kiyofumi Yamamoto, Yoshiyuki Oi, Noriaki Koshikawa, Masayuki Kobayashi
The insular cortex (IC) plays a principal role in the regulation of pain processing. Although opioidergic agonists depress cortical excitatory synaptic transmission, little is known about opioidergic roles in inhibitory synaptic transmission. In the IC, the opioid receptors differentially regulate the excitatory propagation: agonists of the mu (MOR), delta (DOR), and kappa (KOR) exhibit suppressive, facilitative, and little effects, respectively. Thus, we aimed to examine the effects of opioid receptor agonists on unitary inhibitory postsynaptic currents (uIPSCs) in the IC...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27718057/delta-opioid-pharmacology-in-parkinson-s-disease
#15
Omar S Mabrouk
Parkinson's disease (PD) is a progressive neurodegenerative disorder that compromises multiple neurochemical substrates including dopamine, norepinephrine, serotonin, acetylcholine, and glutamate systems. Loss of these transmitter systems initiates a cascade of neurological deficits beginning with motor function and ending with dementia. Current therapies primarily address the motor symptoms of the disease via dopamine replacement therapy. Exogenous dopamine replacement brings about additional challenges since after years of treatment it almost invariably gives rise to dyskinesia as a side effect...
October 8, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27688945/kappa-opioid-receptors-differentially-regulate-low-and-high-levels-of-ethanol-intake-in-female-mice
#16
Ashlee Van't Veer, Karen L Smith, Bruce M Cohen, William A Carlezon, Anita J Bechtholt
INTRODUCTION: Studies in laboratory animals and humans indicate that endogenous opioids play an important role in regulating the rewarding value of various drugs, including ethanol (EtOH). Indeed, opioid antagonists are currently a front-line treatment for alcoholism in humans. Although roles for mu- and delta-opioid receptors have been characterized, the contribution of kappa-opioid receptors (KORs) is less clear. There is evidence that changes in KOR system function can decrease or increase EtOH drinking, depending on test conditions...
September 2016: Brain and Behavior
https://www.readbyqxmd.com/read/27664554/variants-of-opioid-system-genes-are-associated-with-non-dependent-opioid-use-and-heroin-dependence
#17
Matthew Randesi, Wim van den Brink, Orna Levran, Peter Blanken, Eduardo R Butelman, Vadim Yuferov, Joel Correa da Rosa, Jurg Ott, Jan M van Ree, Mary Jeanne Kreek
BACKGROUND: Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. METHODS: Genetic information from four subject groups was collected: non-dependent opioid users (NOD) [n=163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n=143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n=153]...
September 5, 2016: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/27660244/constitutive-desensitization-of-opioid-receptors-in-peripheral-sensory-neurons
#18
Laura C Sullivan, Teresa S Chavera, Raehannah J Jamshidi, Kelly A Berg, William P Clarke
Opioid receptors expressed by peripheral pain-sensing neurons are functionally inactive for antinociceptive signaling under most basal conditions; however, tissue damage or exposure to inflammatory mediators (e.g., bradykinin) converts these receptors from a nonresponsive state to a functionally competent state. Here we tested the hypothesis that the basal, nonresponsive state of the mu- and delta-opioid receptors (MOR and DOR, respectively) is the result of constitutive receptor activity that activates desensitization mechanisms, resulting in MOR and DOR receptor systems that are constitutively desensitized...
December 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27648372/pet-imaging-reveals-sex-differences-in-kappa-opioid-receptor-availability-in-humans-in-vivo
#19
Aishwarya Vijay, Shuo Wang, Patrick Worhunsky, Ming-Qiang Zheng, Nabeel Nabulsi, Jim Ropchan, Suchitra Krishnan-Sarin, Yiyun Huang, Evan D Morris
Opioid receptors may play critical roles in alcoholism and other addictions, addiction withdrawal, and depression and are considered pharmacological targets for treatment of these conditions. Sex differences have been demonstrated in mu (MOR) and delta (DOR) opioid receptors in humans, in vivo. In addition, sex differences have been observed in efficacy of treatment targeting kappa opioid receptors (KOR). Our goal in the present study was to compare the availability of KOR (1) between healthy control (HC) men and women...
2016: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27637375/antinociceptive-effects-of-the-6-o-sulfate-ester-of-morphine-in-normal-and-diabetic-rats-comparative-role-of-mu-and-delta-opioid-receptors
#20
Jai Shankar K Yadlapalli, Benjamin M Ford, Amit Ketkar, Anqi Wan, Narasimha R Penthala, Robert L Eoff, Paul L Prather, Maxim Dobretsov, Peter A Crooks
: This study determined the antinociceptive effects of morphine and morphine-6-O-sulfate (M6S) in both normal and diabetic rats, and evaluated the comparative role of mu-opioid receptors (mu-ORs) and delta-opioid receptors (delta-ORs) in the antinociceptive action of these opioids. In vitro characterization of mu-OR and delta-OR-mediated signaling by M6S and morphine in stably transfected Chinese hamster ovary (CHO-K1) cells showed that M6S exhibited a 6-fold higher affinity for delta-ORs and modulated G-protein and adenylyl cyclase activity via delta-ORs more potently than morphine...
November 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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