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Dopamine Cannabinoids

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https://www.readbyqxmd.com/read/28766743/mouse-retinal-ganglion-cell-signalling-is-dynamically-modulated-through-parallel-anterograde-activation-of-cannabinoid-and-vanilloid-pathways
#1
Andrew O Jo, Jennifer M Noel, Monika Lakk, Oleg Yarishkin, Daniel A Ryskamp, Koji Shibasaki, Maureen A McCall, David Križaj
How retinal ganglion cells (RGCs) process and integrate synaptic, mechanical, swelling stimuli with light inputs is an area of intense debate. The nociceptive cation channel TRPV1 (transient receptor potential vanilloid type 1) modulates RGC Ca(2+) signals and excitability yet the proportion of RGCs that express it remains unclear. Further, TRPV1's response to endocannabinoids (eCBs), the putative endogenous retinal activators unknown, as is the potential modulation by cannabinoid receptors (CBRs). The expression of TRPV1 in RGCs from the Ai9:Trpv1 reporter mouse was nonuniform with peak density in the early- and mid-peripheral retina...
August 2, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28734930/bidirectional-allosteric-interactions-between-cannabinoid-receptor-1-cb1-and-dopamine-receptor-2-long-d2l-heterotetramers
#2
Amina M Bagher, Robert B Laprairie, J Thomas Toguri, Melanie E M Kelly, Eileen M Denovan-Wright
Type 1 cannabinoid (CB1) and dopamine 2 long form (D2L) receptors can physically interact to form heteromers that display unique pharmacology in vitro compared to homomeric complexes. Co-expression of CB1 and D2L and co-application of CB1 and D2 agonists increases cAMP levels while administration of either agonist alone decreases cAMP levels. To understand the observed co-agonist response, our first goal of the current study was to define the stoichiometry of CB1/D2L/Gα protein complexes. Using bioluminescence resonance energy transfer 2 (BRET(2)), we confirmed that, CB1 homodimers, D2L homodimers, and CB1/D2L heteromers are formed...
July 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28734904/identifying-novel-members-of-the-wntless-interactome-through-genetic-and-candidate-gene-approaches
#3
Jessica Petko, Trevor Tranchina, Goral Patel, Robert Levenson, Stephanie Justice-Bitner
Wnt signaling is an important pathway that regulates several aspects of embryogenesis, stem cell maintenance, and neural connectivity. We have recently determined that opioids decrease Wnt secretion, presumably by inhibiting the recycling of the Wnt trafficking protein Wntless (Wls). This effect appears to be mediated by protein-protein interaction between Wls and the mu-opioid receptor (MOR), the primary cellular target of opioid drugs. The goal of this study was to identify novel protein interactors of Wls that are expressed in the brain and may also play a role in reward or addiction...
July 20, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28733540/am1241-alleviates-mptp-induced-parkinson-s-disease-and-promotes-the-regeneration-of-da-neurons-in-pd-mice
#4
Jun Shi, Qiong Cai, Jingxing Zhang, Xiaolie He, Yigang Liu, Rongrong Zhu, Lingjing Jin
The main pathological feature of Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra. In this study, we investigated the role of cannabinoid receptor 2 (CB2R) agonist AM1241 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a mouse model of PD. Upon treatment with AM1241, the decreased CB2R level in the PD mouse brain was reversed and the behavior score markedly elevated, accompanied with a dose-dependent increase of dopamine and serotonin. In addition, western blot assay and immunostaining results suggested that AM1241 significantly activated PI3K/Akt/MEK phosphorylation and increased the expression of Parkin and PINK1, both in the substantia nigra and hippocampus...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28728428/consequence-of-dopamine-d2-receptor-blockade-on-the-hyperphagic-effect-induced-by-cannabinoid-cb1-and-cb2-receptors-in-layers
#5
M Khodadadi, M Zendehdel, A Baghbanzadeh, V Babapour
1. Endocannabinoids (ECBs) and their receptors play a regulatory function on several physiological processes such as feed intake behaviour, mainly in the brain. This study was carried out in order to investigate the effects of the dopaminergic D1 and D2 receptors on CB1/CB2 ECB receptor induced hyperphagia in 3-h feed-deprived (FD3) neonatal layer chickens. 2. A total of 8 experiments were designed to explore the interplay of these two modulatory systems on feed intake in neonatal chickens. In Experiment 1, chickens were intracerebroventricular (ICV) injected with control solution, L-DOPA (levo-dihydroxyphenylalanine as precursor of dopamine; 125 nmol), 2-AG (2-arachidonoylglycerol as CB1 receptor agonist; 2 µg) and co-adminstration of L-DOPA (125 nmol) plus 2-AG (2 µg)...
July 21, 2017: British Poultry Science
https://www.readbyqxmd.com/read/28701511/n-arachidonoyl-dopamine-modulates-acute-systemic-inflammation-via-nonhematopoietic-trpv1
#6
Samira K Lawton, Fengyun Xu, Alphonso Tran, Erika Wong, Arun Prakash, Mark Schumacher, Judith Hellman, Kevin Wilhelmsen
N-Arachidonoyl dopamine (NADA) is an endogenous lipid that potently activates the transient receptor potential vanilloid 1 (TRPV1), which mediates pain and thermosensation. NADA is also an agonist of cannabinoid receptors 1 and 2. We have reported that NADA reduces the activation of cultured human endothelial cells by LPS and TNF-α. Thus far, in vivo studies using NADA have focused on its neurologic and behavioral roles. In this article, we show that NADA potently decreases in vivo systemic inflammatory responses and levels of the coagulation intermediary plasminogen activator inhibitor 1 in three mouse models of inflammation: LPS, bacterial lipopeptide, and polymicrobial intra-abdominal sepsis...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28669034/cannabinoid-reward-and-aversion-effects-in-the-posterior-ventral-tegmental-area-are-mediated-through-dissociable-opiate-receptor-subtypes-and-separate-amygdalar-and-accumbal-dopamine-receptor-substrates
#7
Tasha Ahmad, Steven R Laviolette
RATIONALE: The ventral tegmental area (VTA) and its projections to the basolateral amygdala (BLA) and nucleus accumbens (NAc) are critical for cannabinoid-related motivational effects. Cannabinoid CB1 receptor (CB1R) transmission modulates VTA dopamine (DA) neuron activity and previous reports demonstrate anatomically segregated effects of CB1R transmission in the VTA. However, the underlying pharmacological and anatomical regions responsible for these effects are currently unknown. OBJECTIVES: The objective of the study is to characterize the motivational effects of localized anterior vs...
August 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28660730/fatty-acid-amide-hydrolase-faah-inactivation-confers-enhanced-sensitivity-to-nicotine-induced-dopamine-release-in-the-mouse-nucleus-accumbens
#8
Francisco J Pavon, Antonia Serrano, Nimish Sidhpura, Ilham Polis, David Stouffer, Fernando Rodriguez de Fonseca, Benjamin F Cravatt, Rémi Martin-Fardon, Loren H Parsons
Nicotine exerts its rewarding effects by promoting an increase in dopamine (DA) release in the nucleus accumbens (NAc), and this process is influenced by the endocannabinoid system. Fatty acid amide hydrolase (FAAH) is the main enzyme responsible for the degradation of the endocannabinoid anandamide and other non-cannabinoid N-acylethanolamines. Previous research has reported that both genetic deletion and pharmacological inhibition of FAAH enhance nicotine-induced conditioned place preference at low doses...
June 29, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28653666/endocannabinoid-regulation-of-reward-and-reinforcement-through-interaction-with-dopamine-and-endogenous-opioid-signaling
#9
J M Wenzel, J F Cheer
The endocannabinoid system (eCB) is implicated in the mediation of both reward and reinforcement. This is evidenced by the ability of exogenous cannabinoid drugs to produce hedonia and maintain self-administration in both human and animal subjects. eCBs similarly facilitate behaviors motivated by reward through interaction with the mesolimbic dopamine (DA) and endogenous opioid systems. Indeed, eCB signaling in the ventral tegmental area (VTA) stimulates activation of midbrain DA cells and promotes DA release in terminal regions such as the nucleus accumbens (NAc)...
June 27, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28634109/cannabis-associated-psychosis-neural-substrate-and-clinical-impact
#10
REVIEW
R M Murray, A Englund, A Abi-Dargham, D A Lewis, M Di Forti, C Davies, M Sherif, P McGuire, D C D'Souza
Prospective epidemiological studies have consistently demonstrated that cannabis use is associated with an increased subsequent risk of both psychotic symptoms and schizophrenia-like psychoses. Early onset of use, daily use of high-potency cannabis, and synthetic cannabinoids carry the greatest risk. The risk-increasing effects are not explained by shared genetic predisposition between schizophrenia and cannabis use. Experimental studies in healthy humans show that cannabis and its active ingredient, delta-9-tetrahydrocannabinol (THC), can produce transient, dose-dependent, psychotic symptoms, as well as an array of psychosis-relevant behavioral, cognitive and psychophysiological effects; the psychotogenic effects can be ameliorated by cannabidiol (CBD)...
June 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28619471/oral-haloperidol-or-olanzapine-intake-produces-distinct-and-region-specific-increase-in-cannabinoid-receptor-levels-that-is-prevented-by-high-fat-diet
#11
Foteini Delis, Lauren Rosko, Aditya Shroff, Kenneth E Leonard, Panayotis K Thanos
Clinical studies show higher levels of cannabinoid CB1 receptors (CB1R) in the brain of schizophrenic patients while preclinical studies report a significant functional interaction between dopamine D2 receptors and CB1Rs as well as an upregulation of CB1Rs after antipsychotic treatment. These findings prompted us to study the effects of chronic oral intake of a first and a second generation antipsychotic, haloperidol and olanzapine, on the levels and distribution of CB1Rs in the rat brain. Rats consumed either regular chow or high-fat food and drank water, haloperidol drinking solution (1...
June 13, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28579186/endocannabinoid-modulation-of-homeostatic-and-non-homeostatic-feeding-circuits
#12
REVIEW
Benjamin K Lau, Daniela Cota, Luigia Cristino, Stephanie L Borgland
The endocannabinoid system has emerged as a key player in the control of eating. Endocannabinoids, including 2-arachidonoylglycerol (2-AG) and anandamide (AEA), modulate neuronal activity via cannabinoid 1 receptors (CB1Rs) in multiple nuclei of the hypothalamus to induce or inhibit food intake depending on nutritional and hormonal status, suggesting that endocannabinoids may act in the hypothalamus to integrate different types of signals informing about the animal's energy needs. In the mesocorticolimbic system, (endo)cannabinoids modulate synaptic transmission to promote dopamine release in response to palatable food...
June 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28577135/a-review-of-adjunctive-cns-medications-used-for-the-treatment-of-post-surgical-pain
#13
REVIEW
Ajit Rai, Howard Meng, Aliza Weinrib, Marina Englesakis, Dinesh Kumbhare, Liza Grosman-Rimon, Joel Katz, Hance Clarke
Inadequate post-operative pain management can have significant impacts on patients' quality of life. Effective management of acute pain after surgery is important for early mobilization and discharge from hospital, patient satisfaction, and overall well-being. Utilizing multimodal analgesic strategies has become the mainstay of acute post-operative pain management. A comprehensive search was performed, assessing the published or otherwise publically available literature on different central nervous system (CNS) drugs [excluding opioids, non-steroidal anti-inflammatory drugs (NSAIDs), and acetaminophen] and their uses to treat acute post-surgical pain...
July 2017: CNS Drugs
https://www.readbyqxmd.com/read/28516479/g%C3%AE-s-signalling-of-the-cb1-receptor-and-the-influence-of-receptor-number
#14
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 receptor signalling is canonically mediated through inhibitory Gαi proteins, but occurs through other G proteins under some circumstances, Gαs being the most characterized secondary pathway. Determinants of this signalling switch identified to date include Gαi blockade, CB1 /D2 receptor co-stimulation, CB1 agonist class and cell background. Hence, we examined the effects of receptor number and different ligands on CB1 receptor signalling. EXPERIMENTAL APPROACH: CB1 receptors were expressed in HEK cells at different levels, and signalling characterized for cAMP by real-time BRET biosensor -CAMYEL - and for phospho-ERK by AlphaScreen...
August 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28438833/the-g-protein-gi1-exhibits-basal-coupling-but-not-preassembly-with-g-protein-coupled-receptors
#15
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 the high rate of Gi/o signal transduction have been hypothesized to be enabled by the 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, GABAB, cannabinoid receptor type 1 (CB1R), and dopamine receptor type 2...
June 9, 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
#16
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 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28408985/new-drugs-in-psychiatry-focus-on-new-pharmacological-targets
#17
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
#18
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...
June 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
#19
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-arrestin-2-in-drug-abuse
#20
REVIEW
Kirsten A Porter-Stransky, David Weinshenker
The protein β-arrestin (βarr) 2 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 it 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...
June 2017: Journal of Pharmacology and Experimental Therapeutics
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