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Dopamine Cannabinoids

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https://www.readbyqxmd.com/read/28516479/g%C3%AE-s-signalling-of-the-cb1-receptor-and-the-influence-of-receptor-number
#1
David B Finlay, Erin E Cawston, Natasha L Grimsey, Morag R Hunter, Anisha Korde, V Kiran Vemuri, Alexandros Makriyannis, Michelle Glass
BACKGROUND AND PURPOSE: CB1 cannabinoid receptor signalling is canonically mediated through inhibitory Gαi proteins, but signalling through other G proteins occurs under some circumstances; Gαs being the most characterised secondary pathway. Determinants of this signalling switch identified to date include Gαi blockade, CB1 /D2 dopamine receptor co-stimulation, CB1 agonist class, and cell background. The aim of this study was to examine the effects of receptor number and ligand dependence on CB1 signalling...
May 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28438833/g-protein-gi1-exhibits-basal-coupling-but-not-preassembly-with-g-protein-coupled-receptors
#2
Alexey Bondar, Josef Lazar
The Gi/o protein family transduces signals from a diverse group of G protein-coupled receptors (GPCRs). The observed specificity of Gi/o-GPCR coupling and high rate of Gi/o signal transduction have been hypothesized to be enabled by existence of stable associates between Gi/o proteins and their cognate GPCRs in the inactive state (Gi/o-GPCR preassembly). To test this hypothesis, we applied the recently developed technique of two-photon polarization microscopy (2PPM) to Gαi1 subunits labeled with fluorescent proteins and four GPCRs (the α2A-adrenergic receptor (α2A-AR), γ-aminobutyric acid receptor B (GABAB), cannabinoid receptor type 1 (CB1R) and dopamine receptor type 2 (D2R))...
April 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28409931/1-4-18-f-fluorobenzyl-4-tetrahydrofuran-2-yl-methyl-piperazine-a-novel-suitable-radioligand-with-low-lipophilicity-for-imaging-%C3%AF-1-receptors-in-the-brain
#3
Yingfang He, Fang Xie, Jiajun Ye, Winnie Deuther-Conrad, Bixiao Cui, Liang Wang, Jie Lu, Jörg Steinbach, Peter Brust, Yiyun Huang, Jie Lu, Hongmei Jia
We have designed and synthesized novel piperazine compounds with low lipophilicity as σ1 receptor ligands. 1-(4-Fluorobenzyl)-4-[(tetrahydrofuran-2-yl)methyl]piperazine (10) possessed a low nanomolar σ1 receptor affinity and a high selectivity toward the vesicular acetylcholine transporter (>2000-fold), σ2 receptors (52-fold), and adenosine A2A, adrenergic α2, cannabinoid CB1, dopamine D1, D2L, γ-aminobutyric acid A (GABAA), NMDA, melatonin MT1, MT2, and serotonin 5-HT1 receptors. The corresponding radiotracer [(18)F]10 demonstrated high brain uptake and extremely high brain-to-blood ratios in biodistribution studies in mice...
May 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28408985/new-drugs-in-psychiatry-focus-on-new-pharmacological-targets
#4
REVIEW
Filippo Caraci, Gian Marco Leggio, Salvatore Salomone, Filippo Drago
The approval of psychotropic drugs with novel mechanisms of action has been rare in recent years. To address this issue, further analysis of the pathophysiology of neuropsychiatric disorders is essential for identifying new pharmacological targets for psychotropic medications. In this report, we detail drug candidates being examined as treatments for psychiatric disorders. Particular emphasis is placed on agents with novel mechanisms of action that are being tested as therapies for depression, schizophrenia, or Alzheimer's disease...
2017: F1000Research
https://www.readbyqxmd.com/read/28400256/n-oleoyldopamine-modulates-activity-of-midbrain-dopaminergic-neurons-through-multiple-mechanisms
#5
Olga A Sergeeva, Roberto De Luca, Karolina Mazur, Aissa N Chepkova, Helmut L Haas, Andreas Bauer
N-oleoyl-dopamine (OLDA) is an amide of dopamine and oleic acid, synthesized in catecholaminergic neurons. The present study investigates OLDA targets in midbrain dopaminergic (DA) neurons. Substantia Nigra compacta (SNc) DA neurons recorded in brain slices were excited by OLDA in wild type mice. In transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, however, SNc DA neurons displayed sustained inhibition of firing. In the presence of the dopamine type 2 receptor (D2R) antagonist sulpiride or the dopamine transporter blocker nomifensine no such inhibition was observed...
April 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28363605/genetic-or-pharmacological-depletion-of-cannabinoid-cb1-receptor-protects-against-dopaminergic-neurotoxicity-induced-by-methamphetamine-in-mice
#6
Duy-Khanh Dang, Eun-Joo Shin, Anh-Thu Mai, Choon-Gon Jang, Seung-Yeol Nah, Ji Hoon Jeong, Catherine Ledent, Tsuneyuki Yamamoto, Toshitaka Nabeshima, Emmanuel S Onaivi, Hyoung-Chun Kim
Accumulating evidence suggests that cannabinoid ligands play delicate roles in cell survival and apoptosis decisions, and that cannabinoid CB1 receptors (CB1R) modulate dopaminergic function. However, the role of CB1R in methamphetamine (MA)-induced dopaminergic neurotoxicity in vivo remains elusive. Multiple high doses of MA increased phospho-ERK and CB1R mRNA expressions in the striatum of CB1R (+/+) mice. These increases were attenuated by CB1R antagonists (i.e., AM251 and rimonabant), an ERK inhibitor (U0126), or dopamine D2R antagonist (sulpiride)...
March 29, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28302862/arresting-the-development-of-addiction-the-role-of-%C3%AE-arrestin2-in-drug-abuse
#7
Kirsten A Porter-Stransky, David Weinshenker
The protein β-arrestin2 (βarr2) directly interacts with receptors and signaling pathways that mediate the behavioral effects of drugs of abuse, making it a prime candidate for therapeutic interventions. βarr2 drives desensitization and internalization of G protein-coupled receptors, including dopamine, opioid, and cannabinoid receptors, and can also trigger G protein-independent intracellular signaling. βarr2 mediates several drug-induced behaviors, but the relationship is complex and dependent on the type of behavior (e...
March 16, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28262417/cell-autonomous-excitation-of-midbrain-dopamine-neurons-by-endocannabinoid-dependent-lipid-signaling
#8
Stephanie C Gantz, Bruce P Bean
The major endocannabinoid in the mammalian brain is the bioactive lipid 2-arachidonoylglycerol (2-AG). The best-known effects of 2-AG are mediated by G-protein-coupled cannabinoid receptors. In principle, 2-AG could modify neuronal excitability by acting directly on ion channels, but such mechanisms are poorly understood. Using a preparation of dissociated mouse midbrain dopamine neurons to isolate effects on intrinsic excitability, we found that 100 nM 2-AG accelerated pacemaking and steepened the frequency-current relationship for burst-like firing...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28235999/concise-review-of-the-management-of-iatrogenic-emesis-using-cannabinoids-emphasis-on-nabilone-for-chemotherapy-induced-nausea-and-vomiting
#9
REVIEW
Joseph V Pergolizzi, Robert Taylor, Jo Ann LeQuang, Gianpietro Zampogna, Robert B Raffa
Chemotherapy-induced nausea and vomiting (CINV) is a prevalent, distressing, and burdensome side effect of cancer chemotherapy. It is estimated to affect the majority of patients receiving certain anti-cancer drug regimens and can be treatment-limiting, even for life-saving medications. Despite seemingly numerous options, such as antimuscarinic anticholinergics, antihistamines, 5-HT3 receptor antagonists, dopamine receptor antagonists, and neurokinin-1 receptor antagonists, preventative therapies are often inadequately effective, particularly for "delayed CINV"-leaving an important unmet clinical need...
March 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28222356/extinction-of-avoidance-behavior-by-safety-learning-depends-on-endocannabinoid-signaling-in-the-hippocampus
#10
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/28209735/the-epac-phospholipase-c%C3%AE%C2%B5-pathway-regulates-endocannabinoid-signaling-and-cocaine-induced-disinhibition-of-ventral-tegmental-area-dopamine-neurons
#11
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...
March 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28139681/attenuating-nicotine-reinforcement-and-relapse-by-enhancing-endogenous-brain-levels-of-kynurenic-acid-in-rats-and-squirrel-monkeys
#12
Maria E Secci, Alessia Auber, Leigh V Panlilio, Godfrey H Redhi, Eric B Thorndike, Charles W Schindler, Robert Schwarcz, Steven R Goldberg, Zuzana Justinova
The currently available antismoking medications have limited efficacy and often fail to prevent relapse. Thus, there is a pressing need for newer, more effective treatment strategies. Recently, we demonstrated that enhancing endogenous levels of kynurenic acid (KYNA, a neuroinhibitory product of tryptophan metabolism) counteracts the rewarding effects of cannabinoids by acting as a negative allosteric modulator of α7 nicotinic receptors (α7nAChRs). As the effects of KYNA on cannabinoid reward involve nicotinic receptors, in the present study we used rat and squirrel monkey models of reward and relapse to examine the possibility that enhancing KYNA can counteract the effects of nicotine...
March 1, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28108358/neurochemical-and-metabolic-effects-of-acute-and-chronic-alcohol-in-the-human-brain-studies-with-positron-emission-tomography
#13
REVIEW
Nora D Volkow, Corinde E Wiers, Ehsan Shokri-Kojori, Dardo Tomasi, Gene-Jack Wang, Ruben Baler
The use of Positron emission tomography (PET) to study the effects of acute and chronic alcohol on the human brain has enhanced our understanding of the mechanisms underlying alcohol's rewarding effects, the neuroadaptations from chronic exposure that contribute to tolerance and withdrawal, and the changes in fronto-striatal circuits that lead to loss of control and enhanced motivation to drink that characterize alcohol use disorders (AUD). These include studies showing that alcohol's reinforcing effects may result not only from its enhancement of dopaminergic, GABAergic and opioid signaling but also from its caloric properties...
January 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28092019/urb597-and-the-cannabinoid-win55-212-2-reduce-behavioral-and-neurochemical-deficits-induced-by-mptp-in-mice-possible-role-of-redox-modulation-and-nmda-receptors
#14
Angel Escamilla-Ramírez, Esperanza García, Guadalupe Palencia-Hernández, Ana Laura Colín-González, Sonia Galván-Arzate, Isaac Túnez, Julio Sotelo, Abel Santamaría
Several physiological events in the brain are regulated by the endocannabinoid system (ECS). While synthetic cannabinoid receptor (CBr) agonists such as WIN55,212-2 act directly on CBr, agents like URB597, a fatty acid amide hydrolase (FAAH) inhibitor, induce a more "physiological" activation of CBr by increasing the endogenous levels of the endocannabinoid anandamide (AEA). Herein, we compared the pre- and post-treatment efficacy of URB597 and WIN55,212-2 on different endpoints evaluated in the toxic model produced by the mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice...
May 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28065934/brain-cannabinoid-receptor-2-expression-function-and-modulation
#15
REVIEW
De-Jie Chen, Ming Gao, Fen-Fei Gao, Quan-Xi Su, Jie Wu
Cannabis sativa (marijuana) is a fibrous flowering plant that produces an abundant variety of molecules, some with psychoactive effects. At least 4% of the world's adult population uses cannabis annually, making it one of the most frequently used illicit drugs in the world. The psychoactive effects of cannabis are mediated primarily through cannabinoid receptor (CBR) subtypes. The prevailing view is that CB1Rs are mainly expressed in the central neurons, whereas CB2Rs are predominantly expressed in peripheral immune cells...
March 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28065797/characterising-the-developmental-profile-of-hesc-derived-medium-spiny-neuron-progenitors-and-assessing-mature-neuron-function-using-a-crispr-generated-human-darpp-32-wt-egfp-amp-reporter-line
#16
C P J Hunt, C W Pouton, J M Haynes
In the developing ventral telencephalon, cells of the lateral ganglionic eminence (LGE) give rise to all medium spiny neurons (MSNs). This development occurs in response to a highly orchestrated series of morphogenetic stimuli that pattern the resultant neurons as they develop. Striatal MSNs are characterised by expression of dopamine receptors, dopamine-and cyclic AMP-regulated phosphoprotein (DARPP32) and the neurotransmitter GABA. In this study, we demonstrate that fine tuning WNT and SHH signaling early in human embryonic stem cell differentiation can induce a subpallial progenitor molecular profile...
January 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28017790/the-cb1-receptor-is-required-for-the-establishment-of-the-hyperlocomotor-phenotype-in-developmentally-induced-hypothyroidism-in-mice
#17
Elena Giné, Victor Echeverry-Alzate, Jose Antonio Lopez-Moreno, Fernando Rodriguez de Fonseca, Ana Perez-Castillo, Angel Santos
Alterations in motor functions are well-characterized features observed in humans and experimental animals with thyroid hormone dysfunctions during development. We have previously suggested the implication of the endocannabinoid system in the hyperlocomotor phenotype observed in developmentally induced hypothyroidism in rats. In this work we have further analyzed the implication of endocannabinoids in the effect of hypothyroidism on locomotor activity. To this end, we evaluated the locomotor activity in adult mice lacking the cannabinoid receptor type 1 (CB1R(-/-)) and in their wild type littermates (CB1R(+/+)), whose hypothyroidism was induced in day 12 of gestation and maintained during the experimental period...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28000146/cannabinoid-hyperemesis-syndrome-diagnosis-pathophysiology-and-treatment-a-systematic-review
#18
REVIEW
Cecilia J Sorensen, Kristen DeSanto, Laura Borgelt, Kristina T Phillips, Andrew A Monte
Cannabinoid hyperemesis syndrome (CHS) is a syndrome of cyclic vomiting associated with cannabis use. Our objective is to summarize the available evidence on CHS diagnosis, pathophysiology, and treatment. We performed a systematic review using MEDLINE, Ovid MEDLINE, Embase, Web of Science, and the Cochrane Library from January 2000 through September 24, 2015. Articles eligible for inclusion were evaluated using the Grading and Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Data were abstracted from the articles and case reports and were combined in a cumulative synthesis...
March 2017: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/27988368/conditioned-flavor-preferences-in-animals-merging-pharmacology-brain-sites-and-genetic-variance
#19
Richard J Bodnar
The elucidation of the behavioral, neurochemical, neuroanatomical and genetic substrates mediating the development of conditioned flavor preferences (CFP) is one of the multi-faceted scientific contributions that Dr. Anthony Sclafani has made to the study of food intake. This review summarizes the results of thirty-five publications over nearly twenty years of collaborations between the Sclafani and Bodnar laboratories. This includes the different approaches employed to study the orosensory (flavor-flavor) and post-ingestive (flavor-nutrient) processes underlying CFP including its acquisition (learning) and expression...
December 14, 2016: Appetite
https://www.readbyqxmd.com/read/27853201/the-effects-of-%C3%AE-9-tetrahydrocannabinol-on-the-dopamine-system
#20
REVIEW
Michael A P Bloomfield, Abhishekh H Ashok, Nora D Volkow, Oliver D Howes
The effects of Δ(9)-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, are a pressing concern for global mental health. Patterns of cannabis use are changing drastically owing to legalization, the availability of synthetic analogues (commonly termed spice), cannavaping and an emphasis on the purported therapeutic effects of cannabis. Many of the reinforcing effects of THC are mediated by the dopamine system. Owing to the complexity of the cannabinoid-dopamine interactions that take place, there is conflicting evidence from human and animal studies concerning the effects of THC on the dopamine system...
November 17, 2016: Nature
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