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https://www.readbyqxmd.com/read/27899885/interacting-cannabinoid-and-opioid-receptors-in-the-nucleus-accumbens-core-control-adolescent-social-play
#1
Antonia Manduca, Olivier Lassalle, Marja Sepers, Patrizia Campolongo, Vincenzo Cuomo, Giovanni Marsicano, Brigitte Kieffer, Louk J M J Vanderschuren, Viviana Trezza, Olivier J J Manzoni
Social play behavior is a highly rewarding, developmentally important form of social interaction in young mammals. However, its neurobiological underpinnings remain incompletely understood. Previous work has suggested that opioid and endocannabinoid neurotransmission interact in the modulation of social play. Therefore, we combined behavioral, pharmacological, electrophysiological, and genetic approaches to elucidate the role of the endocannabinoid 2-arachidonoylglycerol (2-AG) in social play, and how cannabinoid and opioid neurotransmission interact to control social behavior in adolescent rodents...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27886263/nicotinic-and-opioid-receptor-regulation-of-striatal-dopamine-d2-receptor-mediated-transmission
#2
Aphroditi A Mamaligas, Yuan Cai, Christopher P Ford
In addition to dopamine neuron firing, cholinergic interneurons (ChIs) regulate dopamine release in the striatum via presynaptic nicotinic receptors (nAChRs) on dopamine axon terminals. Synchronous activity of ChIs is necessary to evoke dopamine release through this pathway. The frequency-dependence of disynaptic nicotinic modulation has led to the hypothesis that nAChRs act as a high-pass filter in the dopaminergic microcircuit. Here, we used optogenetics to selectively stimulate either ChIs or dopamine terminals directly in the striatum...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27877102/inhibition-of-gabaergic-neurotransmission-by-hiv-1-tat-and-opioid-treatment-in-the-striatum-involves-%C3%AE-opioid-receptors
#3
Changqing Xu, Sylvia Fitting
Due to combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic disease with high prevalence of mild forms of neurocognitive impairments, also referred to as HIV-associated neurocognitive disorders (HAND). Although opiate drug use can exacerbate HIV-1 Tat-induced neuronal damage, it remains unknown how and to what extent opioids interact with Tat on the GABAergic system. We conducted whole-cell recordings in mouse striatal slices and examined the effects of HIV-1 Tat in the presence and absence of morphine (1 μM) and damgo (1 μM) on GABAergic neurotransmission...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27827371/sex-differences-in-%C3%AE-opioid-receptor-regulation-of-the-rat-locus-coeruleus-and-their-cognitive-consequences
#4
Herminio M Guajardo, Kevin Snyder, Andrew Ho, Rita J Valentino
Stress-related neuropsychiatric pathologies are more prevalent in females compared to males. An important component of the stress response is activation of the locus coeruleus (LC)-norepinephrine system. Because LC activation is tempered by endogenous opioid release during stress, the magnitude of opioid regulation of the LC could determine stress vulnerability. Here we report convergent evidence for decreased μ-opioid receptor (MOR) function in the female rat LC. The selective MOR agonist, DAMGO (10 pg), completely inhibited LC discharge of male, but not female rats and DAMGO (30 pg) produced no further inhibition of female LC neurons...
November 9, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27825896/activation-of-mu-opioid-receptors-in-the-ventral-pallidum-decreases-the-negative-hedonic-evaluation-of-a-conditioned-aversive-taste-in-rats
#5
Tadashi Inui, Tsuyoshi Shimura
Conditioned taste aversion (CTA) causes a shift in the hedonic evaluation of a conditioned stimulus (CS) from positive to negative, and reduces the CS intake. Mu-opioid receptors (MORs) in the ventral pallidum (VP) are known to be involved in the hedonic evaluation of positive rewarding stimuli; however, their involvement in evaluation of a negative aversive stimulus is still unclear. To explore the neural mechanisms of the negative hedonic evaluation of the CS in CTA, we examined the effects of the activation of VP MORs on the behavioral responses of rats to a CS...
November 5, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27743985/mu-opioid-receptor-inhibition-decreases-voluntary-wheel-running-in-a-dopamine-dependent-manner-in-rats-bred-for-high-voluntary-running
#6
Gregory N Ruegsegger, Jacob D Brown, M Cathleen Kovarik, Dennis K Miller, Frank W Booth
The mesolimbic dopamine and opioid systems are postulated to influence the central control of physical activity motivation. We utilized selectively bred rats for high (HVR) or low (LVR) voluntary running behavior to examine (1) inherent differences in mu-opioid receptor (Oprm1) expression and function in the nucleus accumbens (NAc), (2) if dopamine-related mRNAs, wheel-running, and food intake are differently influenced by intraperitoneal (i.p.) naltrexone injection in HVR and LVR rats, and (3) if dopamine is required for naltrexone-induced changes in running and feeding behavior in HVR rats...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27743812/mu-opioid-receptors-in-the-caudomedial-nts-are-critical-for-respiratory-responses-to-stimulation-of-bronchopulmonary-c-fibers-and-carotid-body-in-conscious-rats
#7
Jianguo Zhuang, Xiuping Gao, Franklin Gao, Fadi Xu
We tested the hypothesis that mu-opioid receptors (MORs) in the caudomedial nucleus tractus solitarius (cmNTS) are important for the ventilatory responses to stimulation of bronchopulmonary C-fibers (PCFs), the carotid body-mediated hypoxia, and hypercapnia independent of the carotid body. First, we used immunohistochemistry to map MORs distribution in the caudal medulla. Then we compared the effects of intra-cmNTS microinjection of DAMGO (a MOR agonist) with or without a combination of CTAP (a MOR antagonist) on the ventilatory responses to: 1) right atrial injection of capsaicin (to stimulation of PCFs) and 2) acute hypoxia (HVR, to stimulate the carotid body) in awake intact rats; and 3) hypercapnia (HCVR) in the carotid body ablated rats...
January 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/27725218/opioid-subtype-and-cell-type-dependent-regulation-of-inhibitory-synaptic-transmission-in-the-rat-insular-cortex
#8
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/27660244/constitutive-desensitization-of-opioid-receptors-in-peripheral-sensory-neurons
#9
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/27648914/tetrapeptide-endomorphin-analogs-require-both-full-length-and-truncated-splice-variants-of-the-mu-opioid-receptor-gene-oprm1-for-analgesia
#10
Gina F Marrone, Zhigang Lu, Grace Rossi, Ankita Narayan, Amanda Hunkele, Sarah Marx, Jin Xu, John Pintar, Susruta Majumdar, Ying-Xian Pan, Gavril W Pasternak
The mu opioid receptor gene undergoes extensive alternative splicing. Mu opioids can be divided into three classes based on the role of different groups of splice variants. Morphine and methadone require only full length seven transmembrane (7TM) variants for analgesia, whereas IBNtxA (3'-iodobenzyol-6β-naltrexamide) needs only truncated 6TM variants. A set of endomorphin analogs fall into a third group that requires both 6TM and 7TM splice variants. Unlike morphine, endomorphin 1 and 2, DAPP (Dmt,d-Ala-Phe-Phe-NH2), and IDAPP (3'-iodo-Dmt-d-Ala-Phe-Phe-NH2) analgesia was lost in an exon 11 knockout mouse lacking 6TM variants...
October 10, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27610039/damgo-modulates-two-pore-domain-k-channels-in-the-substantia-gelatinosa-neurons-of-rat-spinal-cord
#11
Pyung Sun Cho, Han Kyu Lee, Sang Hoon Lee, Jay Zoon Im, Sung Jun Jung
The analgesic mechanism of opioids is known to decrease the excitability of substantia gelatinosa (SG) neurons receiving the synaptic inputs from primary nociceptive afferent fiber by increasing inwardly rectifying K(+) current. In this study, we examined whether a µ-opioid agonist, [D-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), affects the two-pore domain K(+) channel (K2P) current in rat SG neurons using a slice whole-cell patch clamp technique. Also we confirmed which subtypes of K2P channels were associated with DAMGO-induced currents, measuring the expression of K2P channel in whole spinal cord and SG region...
September 2016: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/27600870/biased-%C3%AE-opioid-receptor-agonists-diversely-regulate-lateral-mobility-and-functional-coupling-of-the-receptor-to-its-cognate-g-proteins
#12
Barbora Melkes, Lucie Hejnova, Jiri Novotny
There are some indications that biased μ-opioid ligands may diversely affect μ-opioid receptor (MOR) properties. Here, we used confocal fluorescence recovery after photobleaching (FRAP) to study the regulation by different MOR agonists of receptor movement within the plasma membrane of HEK293 cells stably expressing a functional yellow fluorescent protein (YFP)-tagged μ-opioid receptor (MOR-YFP). We found that the lateral mobility of MOR-YFP was increased by (D-Ala(2),N-MePhe(4),Gly(5)-ol)-enkephalin (DAMGO) and to a lesser extent also by morphine but decreased by endomorphin-2...
September 6, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27530869/ignavine-a-novel-allosteric-modulator-of-the-%C3%AE-opioid-receptor
#13
Katsuya Ohbuchi, Chika Miyagi, Yasuyuki Suzuki, Yasuharu Mizuhara, Keita Mizuno, Yuji Omiya, Masahiro Yamamoto, Eiji Warabi, Yuka Sudo, Akinobu Yokoyama, Kanako Miyano, Takatsugu Hirokawa, Yasuhito Uezono
Processed Aconiti tuber (PAT) is used to treat pain associated with various disorders. Although it has been demonstrated that the κ opioid receptor (KOR) signaling pathway is a mediator of the analgesic effect of PAT, active components affecting opioid signaling have not yet been identified. In this study, we explored candidate components of PAT by pharmacokinetic analysis and identified ignavine, which is a different structure from aconitine alkaloids. A receptor binding assay of opioid receptors showed that ignavine specifically binds the μ opioid receptor (MOR), not the KOR...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27511839/acute-stimulation-of-brain-mu-opioid-receptors-inhibits-glucose-stimulated-insulin-secretion-via-sympathetic-innervation
#14
Eva Tudurí, Daniel Beiroa, Johannes Stegbauer, Johan Fernø, Miguel López, Carlos Diéguez, Rubén Nogueiras
Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i...
November 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27510425/low-%C3%AE-opioid-receptor-status-in-alcohol-dependence-identified-by-combined-positron-emission-tomography-and-post-mortem-brain-analysis
#15
Derik Hermann, Natalie Hirth, Matthias Reimold, Anil Batra, Michael N Smolka, Sabine Hoffmann, Falk Kiefer, Hamid R Noori, Wolfgang H Sommer, Gerald Reischl, Christian la Fougère, Karl Mann, Rainer Spanagel, Anita C Hansson
Blockade of the μ-opioid receptor (MOR) by naltrexone reduces relapse risk in a subpopulation of alcohol-dependent patients. Previous positron-emission-tomography (PET) studies using the MOR ligand [(11)C]carfentanil have found increased MOR availability in abstinent alcoholics, which may reflect either increased MOR expression or lower endogenous ligand concentration. To differentiate between both effects, we investigated two cohorts of alcoholic subjects using either post-mortem or clinical PET analysis...
September 21, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27508965/accumbal-%C3%AE-opioid-receptors-modulate-ethanol-intake-in-alcohol-preferring-alko-alcohol-rats
#16
Johanna Uhari-Väänänen, Atso Raasmaja, Pia Bäckström, Ville Oinio, Mikko Airavaara, Petteri Piepponen, Kalervo Kiianmaa
BACKGROUND: The nucleus accumbens shell is a key brain area mediating the reinforcing effects of ethanol (EtOH). Previously, it has been shown that the density of μ-opioid receptors in the nucleus accumbens shell is higher in alcohol-preferring Alko Alcohol (AA) rats than in alcohol-avoiding Alko Non-Alcohol rats. In addition, EtOH releases opioid peptides in the nucleus accumbens and opioid receptor antagonists are able to modify EtOH intake, all suggesting an opioidergic mechanism in the control of EtOH consumption...
October 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27450703/peripheral-interactions-between-cannabinoid-and-opioid-receptor-agonists-in-a-model-of-inflammatory-mechanical-hyperalgesia
#17
Q-Schick Auh, Yang Hyun Chun, Ohannes K Melemedjian, Youping Zhang, Jin Y Ro
Activation of opioid and cannabinoid receptors expressed in nociceptors induces effective antihyperalgesia. In this study, we examined whether combinations of opioid and cannabinoid receptor agonists directed at the injured site would enhance therapeutic effectiveness. Behavioral pharmacology experiments were performed to compare the effects of DAMGO, a selective agonist for μ-opioid receptor (MOR), ACPA, a specific agonist for CB1, and combinations of DAMGO and ACPA in attenuating complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia in the rat hindpaw...
July 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27443980/the-impact-of-%C3%AE-azido-or-1-piperidinyl-methylamino-acids-in-position-2-or-3-on-biological-activity-and-conformation-of-dermorphin-analogues
#18
Maciej Maciejczyk, Anika Lasota, Oliwia Frączak, Piotr Kosson, Aleksandra Misicka, Michał Nowakowski, Andrzej Ejchart, Aleksandra Olma
The synthesis of new dermorphin analogues is described. The (R)-alanine or phenylalanine residues of natural dermorphin were substituted by the corresponding α-methyl-β-azidoalanine or α-benzyl-β-azido(1-piperidinyl)alanine residues. The potency and selectivity of the new analogues were evaluated by a competitive receptor binding assay in rat brain using [(3) H]DAMGO (a μ ligand) and [(3) H]DELT (a δ ligand). The most active analogue in this series, Tyr-(R)-Ala-(R)-α-benzyl-β-azidoAla-Gly-Tyr-Pro-Ser-NH2 and its epimer were analysed by (1) H and (13) C NMR spectroscopy and restrained molecular dynamics simulations...
August 2016: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/27427945/mu-opioid-receptor-actions-in-the-lateral-habenula
#19
Elyssa B Margolis, Howard L Fields
Increased activity of lateral habenula (LHb) neurons is correlated with aversive states including pain, opioid abstinence, rodent models of depression, and failure to receive a predicted reward. Agonists at the mu opioid receptor (MOR) are among the most powerful rewarding and pain relieving drugs. Injection of the MOR agonist morphine directly into the habenula produces analgesia, raising the possibility that MOR acts locally within the LHb. Consequently, we examined the synaptic actions of MOR agonists in the LHb using whole cell patch clamp recording...
2016: PloS One
https://www.readbyqxmd.com/read/27393342/pharmacokinetic-considerations-of-nanodelivery-to-the-brain-using-modeling-and-simulations-to-predict-the-outcome-of-liposomal-formulations
#20
Annika Lindqvist, Markus Fridén, Margareta Hammarlund-Udenaes
The use of nanocarriers is an intriguing solution to increase the brain delivery of novel therapeutics. The aim of this paper was to use pharmacokinetic analysis and simulations to identify key factors that determine the effective drug concentration-time profile at the target site in the brain. Model building and simulations were based on experimental data obtained from the administration of the opioid peptide DAMGO in glutathione tagged PEGylated liposomes to rats. Different pharmacokinetic models were investigated to explore the mechanisms of increased brain delivery...
September 20, 2016: European Journal of Pharmaceutical Sciences
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