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https://www.readbyqxmd.com/read/28222356/extinction-of-avoidance-behavior-by-safety-learning-depends-on-endocannabinoid-signaling-in-the-hippocampus
#1
Vincenzo Micale, Jens Stepan, Angela Jurik, Fabricio A Pamplona, Rudolph Marsch, Filippo Drago, Matthias Eder, Carsten T Wotjak
The development of exaggerated avoidance behavior is largely responsible for the decreased quality of life in patients suffering from anxiety disorders. Studies using animal models have contributed to the understanding of the neural mechanisms underlying the acquisition of avoidance responses. However, much less is known about its extinction. Here we provide evidence in mice that learning about the safety of an environment (i.e., safety learning) rather than repeated execution of the avoided response in absence of negative consequences (i...
February 3, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28220706/human-cannabinoid-receptor-2-ligand-interaction-motif-transmembrane-helix-2-cysteine-c2-59-89-as-determinant-of-classical-cannabinoid-agonist-activity-and-binding-pose
#2
Han Zhou, Yan Peng, Aneetha Halikhedkar, Pusheng Fan, David R Janero, Ganesh A Thakur, Richard Warren Mercier, Xin Sun, Xiaoyu Ma, Alexandros Makriyannis
Cannabinoid receptor 2 (CB2R)-dependent signaling is implicated in neuronal physiology and immune surveillance by brain microglia. Selective CB2R agonists hold therapeutic promise for inflammatory and other neurological disorders. Information on human CB2R (hCB2R) ligand-binding and functional domains is needed to inform the rational design and optimization of candidate drug-like hCB2R agonists. Prior demonstration that hCB2R transmembrane helix 2 (TMH2) cysteine C2.59(89) reacts with small-molecule methanethiosulfonates showed that this cysteine residue is accessible to sulfhydryl derivatization reagents...
February 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28220074/involvement-of-cannabinoid-signaling-in-vincristine-induced-gastrointestinal-dysmotility-in-the-rat
#3
Gema Vera, Ana E López-Pérez, José A Uranga, Rocío Girón, Ma Isabel Martín-Fontelles, Raquel Abalo
Background: In different models of paralytic ileus, cannabinoid receptors are overexpressed and endogenous cannabinoids are massively released, contributing to gastrointestinal dysmotility. The antitumoral drug vincristine depresses gastrointestinal motility and a similar mechanism could participate in this effect. Therefore, our aim was to determine, using CB1 and CB2 antagonists, whether an increased endocannabinoid tone is involved in vincristine-induced gastrointestinal ileus. Methods: First, we confirmed the effects of vincristine on the gut mucosa, by conventional histological techniques, and characterized its effects on motility, by radiographic means...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28220044/pregnenolone-blocks-cannabinoid-induced-acute-psychotic-like-states-in-mice
#4
A Busquets-Garcia, E Soria-Gómez, B Redon, Y Mackenbach, M Vallée, F Chaouloff, M Varilh, G Ferreira, P-V Piazza, G Marsicano
Cannabis-induced acute psychotic-like states (CIAPS) represent a growing health issue, but their underlying neurobiological mechanisms are poorly understood. The use of antipsychotics and benzodiazepines against CIAPS is limited by side effects and/or by their ability to tackle only certain aspects of psychosis. Thus, safer wide-spectrum treatments are currently needed. Although the blockade of cannabinoid type-1 receptor (CB1) had been suggested as a therapeutical means against CIAPS, the use of orthosteric CB1 receptor full antagonists is strongly limited by undesired side effects and low efficacy...
February 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28219717/effects-of-tetrahydrocannabinol-on-glucose-uptake-in-the-rat-brain
#5
I Miederer, K Uebbing, J Röhrich, S Maus, N Bausbacher, K Krauter, V Weyer-Elberich, B Lutz, M Schreckenberger, R Urban
Δ(9)-Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [(18)F]-fluoro-2-deoxy-d-glucose were injected...
February 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28219703/immunomodulatory-properties-of-1-2-dihydro-4-hydroxy-2-oxo-1-8-naphthyridine-3-carboxamide-derivative-vl15
#6
Anna Maria Malfitano, Chiara Laezza, Simone Bertini, Daniela Marasco, Tiziano Tuccinardi, Maurizio Bifulco, Clementina Manera
1,2-dihydro-4-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide derivative VL15 has been recently developed as a selective cannabinoid CB2 receptor compound. Given the high selectivity of this compound at the cannabinoid CB2 receptor and the well-known protective function of this receptor in neurological disorders with autoimmune component like multiple sclerosis, we assessed the immunomodulatory properties of VL15. We assessed on activated peripheral blood mononuclear cells (PBMC), proliferation and viability, cell cycle progression and measured activation markers and the expression of phosphorylated proteins...
February 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28219487/evidence-for-the-risks-and-consequences-of-adolescent-cannabis-exposure
#7
REVIEW
Amir Levine, Kelly Clemenza, Moira Rynn, Jeffrey Lieberman
OBJECTIVE: This review of the scientific literature examines the potential adult sequelae of exposure to cannabis and related synthetic cannabinoids in adolescence. We examine the four neuropsychiatric outcomes that are likely most vulnerable to alteration by early cannabinoid use, as identified within both the clinical and preclinical research: cognition, emotional functioning, risk for psychosis, and addiction. METHOD: A literature search was conducted through PubMed, PsychInfo, and Google Scholar with no publication date restrictions...
March 2017: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/28218780/microrna-139-modulates-alzheimer-s-associated-pathogenesis-in-samp8-mice-by-targeting-cannabinoid-receptor-type-2
#8
Y Tang, J S Bao, J H Su, W Huang
Alzheimer's disease (AD) is a neurodegenerative disorder, and is the most common type of dementia in the elderly population. Growing evidence indicates that microRNAs (miRNAs) play a crucial role in neuroinflammation associated with AD progression. In this study, we analyzed the expression of microRNA-139 (miR-139) as well as the learning and memory function in AD. We observed that the miR-139 expression was significantly higher in the hippocampus of aged senescence accelerated mouse prone 8 (SAMP8) mice (2...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28218648/expression-purification-and-monitoring-of-conformational-changes-of-hcb2-tmh67h8-in-different-membrane-mimetic-lipid-mixtures-using-circular-dichroism-and-nmr-techniques
#9
Elvis K Tiburu, Jianqin Zhuang, Heidimarie N A Fleischer, Patrick K Arthur, Gordon A Awandare
This work was intended to develop self-assembly lipids for incorporating G-protein coupled receptors (GPCRs) in order to improve the success rate for nuclear magnetic resonance spectroscopy (NMR) structural elucidation. We hereby report the expression and purification of uniformly (15)N-labeled human cannabinoid receptor-2 domain in insect cell media. The domain was refolded by screening several membrane mimetic environments. Different q ratios of isotropic bicelles were screened for solubilizing transmembrane helix 6, 7 and 8 (TMH67H8)...
February 17, 2017: Membranes
https://www.readbyqxmd.com/read/28215997/cannabinoids-and-epilepsy-introduction
#10
EDITORIAL
Jerzy P Szaflarski, Orrin Devinsky
No abstract text is available yet for this article.
February 16, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28215162/gut-brain-axis-role-of-lipids-in-the-regulation-of-inflammation-pain-and-cns-diseases
#11
Roberto Russo, Claudia Cristiano, Carmen Avagliano, Carmen De Caro, Giovanna La Rana, Giuseppina Mattace Raso, Roberto Berni Canani, Rosaria Meli, Antonio Calignano
The human gut is a composite anaerobic environment with a large, diverse and dynamic enteric microbiota, represented by more than 100 trillion microorganisms, including at least 1000 distinct species. The discovery that a different microbial composition can influence behavior and cognition, and in turn the nervous system can indirectly influence enteric microbiota composition, has significantly contributed to establish the well-accepted concept of gut-brain axis. This hypothesis is supported by several evidence showing mutual mechanisms, which involve the vague nerve, the immune system, the hypothalamic-pituitary-adrenal (HPA) axis modulation and the bacteria-derived metabolites...
February 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28214870/the-inhibitory-effect-of-s-777469-a-cannabinoid-type-2-receptor-agonist-on-skin-inflammation-in-mice
#12
Takayo Haruna, Masahiko Soga, Yasuhide Morioka, Kinichi Imura, Yoko Furue, Mina Yamamoto, Jun Hayakawa, Masashi Deguchi, Akinori Arimura, Kiyoshi Yasui
We investigated the effects of S-777469 (1-[[6-Ethyl-1-[4-fluorobenzyl]-5-methyl-2-oxo-1, 2-dihydropyridine-3-carbonyl]amino]-cyclohexanecarboxylic acid), a novel cannabinoid type 2 receptor (CB2) agonist, on 1-fluoro-2,4-dinitrobenzene (DNFB)-induced ear inflammation and mite antigen-induced dermatitis in mice. The oral administration of S-777469 significantly suppressed DNFB-induced ear swelling in a dose-dependent manner. In addition, S-777469 significantly alleviated mite antigen-induced atopic dermatitis-like skin lesions in NC/Nga mice...
February 18, 2017: Pharmacology
https://www.readbyqxmd.com/read/28214755/identification-of-a-new-tert-leucinate-class-synthetic-cannabinoid-in-powder-and-spice-like-herbal-incenses-methyl-2-1-5-fluoropentyl-indole-3-carbonyl-amino-3-3-dimethyl-butanoate-5f-mdmb-pica
#13
Martijn D P Risseeuw, Peter Blanckaert, Vera Coopman, Stijn Van Quekelberghe, Serge Van Calenbergh, Jan Cordonnier
A brown powder and different product packages of "spice-like" herbal incenses were analyzed using a systematic identification approach based on liquid chromatography with diode array detector (HPLC-PDA) and gas chromatography mass spectrometry (GC-MS) with computer based library search against spectral libraries. However, the most predominant compound in the methanolic sample solutions could not be identified. In order to elucidate the chemical structure, a more extensive analysis of the material was initiated using liquid chromatography mass spectrometry (LC-MS), electrospray high resolution mass spectrometry (ESI-HRMS) and (1)H, (13)C and (19)F nuclear magnetic resonance spectroscopy (NMR), which allowed the identification and characterization of the major compound as methyl 2-[[1-(5-fluoropentyl)indole-3-carbonyl]amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA)...
February 4, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28213089/monoglyceride-lipase-as-a-drug-target-at-the-crossroads-of-arachidonic-acid-metabolism-and-endocannabinoid-signaling
#14
REVIEW
Gernot F Grabner, Robert Zimmermann, Rudolf Schicho, Ulrike Taschler
Monoglyerides (MGs) are short-lived, intermediary lipids deriving from the degradation of phospho- and neutral lipids, and monoglyceride lipase (MGL), also designated as monoacylglycerol lipase (MAGL), is the major enzyme catalyzing the hydrolysis of MGs into glycerol and fatty acids. This distinct function enables MGL to regulate a number of physiological and pathophysiological processes since both MGs and fatty acids can act as signaling lipids or precursors thereof. The most prominent MG species acting as signaling lipid is 2-arachidonoylglycerol (2-AG) which is the most abundant endogenous agonist of cannabinoid receptors in the body...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28210722/synthesis-radio-synthesis-and-in-vitro-evaluation-of-terminally-fluorinated-derivatives-of-hu-210-and-hu-211-as-novel-candidate-pet-tracers
#15
Chiara Zanato, Alessia Pelagalli, Katie F M Marwick, Monica Piras, Sergio Dall'Angelo, Andrea Spinaci, Roger G Pertwee, David J A Wyllie, Giles E Hardingham, Matteo Zanda
We report the synthesis of terminally fluorinated HU-210 and HU-211 analogues (HU-210F and HU-211F, respectively) and their biological evaluation as ligands of cannabinoid receptors (CB1 and CB2) and N-methyl d-aspartate receptor (NMDAR). [(18)F]-labelled HU-210F was radiosynthesised from the bromo-substituted precursor. In vitro assays showed that both HU-210F and HU-211F retain the potent pharmacological profile of HU-210 and HU-211, suggesting that [(18)F]-radiolabelled HU-210F and HU-211F could have potential as PET tracers for in vivo imaging...
February 17, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28210207/cannabinoid-receptor-2-signaling-in-neurodegenerative-disorders-from-pathogenesis-to-a-promising-therapeutic-target
#16
REVIEW
Tommaso Cassano, Silvio Calcagnini, Lorenzo Pace, Federico De Marco, Adele Romano, Silvana Gaetani
As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically. Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28209996/transient-cannabinoid-receptor-2-blockade-during-immunization-heightens-intensity-and-breadth-of-antigen-specific-antibody-responses-in-young-and-aged-mice
#17
Emmanuel Dotsey, Irina Ushach, Egest Pone, Rie Nakajima, Algis Jasinskas, Donovan A Argueta, Andrea Dillon, Nicholas DiPatrizio, Huw Davies, Albert Zlotnik, Peter D Crompton, Philip L Felgner
The hallmark of vaccines is their ability to prevent the spread of infectious pathogens and thereby serve as invaluable public health tool. Despite their medical relevance, there is a gap in our understanding of the physiological factors that mediate innate and adaptive immune response to vaccines. The endocannabinoid (eCB) system is a critical modulator of homeostasis in vertebrates. Our results indicate that macrophages and dendritic cells produce the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG) upon antigen activation...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209735/the-epac-phospholipase-c%C3%AE%C2%B5-pathway-regulates-endocannabinoid-signaling-and-cocaine-induced-disinhibition-of-vta-dopamine-neurons
#18
Jiaqing Tong, Xiaojie Liu, Casey Vickstrom, Yan Li, Laikang Yu, Youming Lu, Alan V Smrcka, Qing-Song Liu
Exchange protein directly activated by cAMP (Epac) is a direct effector for the ubiquitous second messenger cAMP. Epac activates the phospholipase Cε (PLCε) pathway. PLCβ has been linked to the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Here, we report that Epac facilitates endocannabinoid-mediated retrograde synaptic depression through activation of PLCε. Intracellular loading of a selective Epac agonist 8-CPT-2Me-cAMP into ventral tegmental area (VTA) dopamine neurons enabled previously ineffective stimuli to induce depolarization-induced suppression of inhibition (DSI) and long-term depression of IPSCs (I-LTD) in the VTA...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28209423/constitutive-increases-in-amygdalar-corticotropin-releasing-factor-and-fatty-acid-amide-hydrolase-drive-an-anxious-phenotype
#19
Luis A Natividad, Matthew W Buczynski, Melissa A Herman, Dean Kirson, Christopher S Oleata, Cristina Irimia, Ilham Polis, Roberto Ciccocioppo, Marisa Roberto, Loren H Parsons
BACKGROUND: Corticotropin-releasing factor (CRF) mediates anxiogenic responses by activating CRF type 1 (CRF1) receptors in limbic brain regions. Anxiety is further modulated by the endogenous cannabinoid (eCB) system that attenuates the synaptic effects of stress. In the amygdala, acute stress activates the enzymatic clearance of the eCB N-arachidonoylethanolamine via fatty acid amide hydrolase (FAAH), although it is unclear whether chronic dysregulation of CRF systems induces maladaptive changes in amygdalar eCB signaling...
January 13, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28207753/analysis-of-diagnoses-extracted-from-electronic-health-records-in-a-large-mental-health-case-register
#20
Yevgeniya Kovalchuk, Robert Stewart, Matthew Broadbent, Tim J P Hubbard, Richard J B Dobson
The UK government has recently recognised the need to improve mental health services in the country. Electronic health records provide a rich source of patient data which could help policymakers to better understand needs of the service users. The main objective of this study is to unveil statistics of diagnoses recorded in the Case Register of the South London and Maudsley NHS Foundation Trust, one of the largest mental health providers in the UK and Europe serving a source population of over 1.2 million people residing in south London...
2017: PloS One
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