keyword
https://read.qxmd.com/read/38514005/food-preference-based-screening-method-for-identification-of-effectors-of-substance-use-disorders-using-caenorhabditis-elegans
#1
JOURNAL ARTICLE
Aaron Taehwan Kim, Sida Li, Yoo Kim, Young-Jai You, Yeonhwa Park
Substance use disorder (SUD) affects over 61 million Americans aged 12 and over. Thus, identifying novel chemicals contributing to SUD will be critical for developing efficient prevention and mitigation strategies. Considering the complexity of the actions and effects of these substances on human behavior, a high-throughput platform using a living organism is ideal. We developed a quick and easy screening assay using Caenorhabditis elegans. C. elegans prefers high-quality food (Escherichia coli HB101) over low-quality food (Bacillus megaterium), with a food preference index of approximately 0...
March 19, 2024: Life Sciences
https://read.qxmd.com/read/38505994/cardiotoxic-effects-of-common-and-emerging-drugs-role-of-cannabinoid-receptors
#2
JOURNAL ARTICLE
Yiming Bo, Xin Zhao, Liliang Li
Drug-induced cardiotoxicity has become one of the most common and detrimental health concerns, which causes significant loss to public health and drug resources. Cannabinoid receptors (CBRs) have recently achieved great attention for their vital roles in the regulation of heart health and disease, with mounting evidence linking CBRs with the pathogenesis and progression of drug-induced cardiotoxicity. This review aims to summarize fundamental characteristics of two well-documented CBRs (CB1R and CB2R) from aspects of molecular structure, signaling and their functions in cardiovascular physiology and pathophysiology...
March 20, 2024: Clinical Science (1979-)
https://read.qxmd.com/read/38482984/adenosine-receptors-are-the-on-and-off-switch-of-astrocytic-cannabinoid-type-1-cb1-receptor-effect-upon-synaptic-plasticity-in-the-medial-prefrontal-cortex
#3
JOURNAL ARTICLE
Joana Gonçalves-Ribeiro, Oksana K Savchak, Sara Costa-Pinto, Joana I Gomes, Rafael Rivas-Santisteban, Alejandro Lillo, Javier Sánchez Romero, Ana M Sebastião, Marta Navarrete, Gemma Navarro, Rafael Franco, Sandra H Vaz
The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca2+ ) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A1 and A2A receptors (A1 R, A2A R), being unknown the crosstalk between CB1R and adenosine receptors in these cells. We show here that a further level of regulation of astrocyte Ca2+ signaling occurs through CB1R-A2A R or CB1R-A1 R heteromers that ultimately impact mPFC synaptic plasticity...
March 14, 2024: Glia
https://read.qxmd.com/read/38479224/err%C3%AE-inducible-fgf23-promotes-alcoholic-liver-injury-through-enhancing-cyp2e1-mediated-hepatic-oxidative-stress
#4
JOURNAL ARTICLE
Yoon Seok Jung, Kamalakannan Radhakrishnan, Seddik Hammad, Sebastian Müller, Johannes Müller, Jung-Ran Noh, Jina Kim, In-Kyu Lee, Sung Jin Cho, Don-Kyu Kim, Yong-Hoon Kim, Chul-Ho Lee, Steven Dooley, Hueng-Sik Choi
Fibroblast growth factor 23 (FGF23) is a member of endocrine FGF family, along with FGF15/19 and FGF21. Recent reports showed that under pathological conditions, liver produces FGF23, although the role of hepatic FGF23 remains nebulous. Here, we investigated the role of hepatic FGF23 in alcoholic liver disease (ALD) and delineated the underlying molecular mechanism. FGF23 expression was compared in livers from alcoholic hepatitis patients and healthy controls. The role of FGF23 was examined in hepatocyte-specific knock-out (LKO) mice of cannabinoid receptor type 1 (CB1R), estrogen related receptor γ (ERRγ), or FGF23...
March 5, 2024: Redox Biology
https://read.qxmd.com/read/38467844/late-adolescent-onset-of-prefrontal-endocannabinoid-control-of-hippocampal-and-amygdalar-inputs-and-its-impact-on-trace-fear-conditioning-behavior
#5
JOURNAL ARTICLE
Hanna M Molla, Anabel M M Miguelez Fernández, Kuei Y Tseng
Prefrontal cortex (PFC) maturation during adolescence is characterized by structural and functional changes, which involve the remodeling of GABA and glutamatergic synapses, as well as changes in the endocannabinoid system. Yet, the way PFC endocannabinoid signaling interacts with local GABA and glutamatergic function to impact its processing of afferent transmission during the adolescent transition to adulthood remains unknown. Here we combined PFC local field potential recordings with local manipulations of 2-AG and anandamide levels to assess how PFC endocannabinoid signaling is recruited to modulate ventral hippocampal and basolateral amygdalar inputs in vivo in adolescent and adult male rats...
March 11, 2024: Neuropsychopharmacology
https://read.qxmd.com/read/38457018/cannabinoids-in-the-treatment-of-glioblastoma
#6
REVIEW
Barbara Buchalska, Katarzyna Kamińska, Maja Owe-Larsson, Agnieszka Cudnoch-Jędrzejewska
Glioblastoma (GBM) is the most prevalent primary malignant tumor of the nervous system. While the treatment of other neoplasms is increasingly more efficacious the median survival rate of GBM patients remains low and equals about 14 months. Due to this fact, there are intensive efforts to find drugs that would help combat GBM. Nowadays cannabinoids are becoming more and more important in the field of cancer and not only because of their properties of antiemetic drugs during chemotherapy. These compounds may have a direct cytotoxic effect on cancer cells...
March 8, 2024: Pharmacological Reports: PR
https://read.qxmd.com/read/38420293/clinical-importance-of-cannabinoid-type-1-receptor-cb1r-and-cannabinoid-type-2-receptor-cb2r-expression-in-renal-cell-carcinoma
#7
JOURNAL ARTICLE
Dimitrios Deligiannis, Ioannis Anastasiou, Dionysios Mitropoulos, Panagiotis Mitsos, Stamatios Theocharis
Background and objective The purpose of our study was to assess the expression of cannabinoid type 1 receptor (CB1R) and cannabinoid type 2 receptor (CB2R), including positivity, intensity, percentage, site of distribution, and immunohistochemical score, in renal cell carcinomas (RCCs) and explore their correlation with various clinicopathological aspects. Methodology We retrospectively obtained data and specimens from 87 patients diagnosed with RCC after partial or radical nephrectomy, and the CB1R and CB2R expression was assessed immunohistochemically on paraffin-embedded tissues...
February 2024: Curēus
https://read.qxmd.com/read/38419882/orexin-and-cannabinoid-systems-modulate-long-term-potentiation-of-the-hippocampus-ca1-area-in-anesthetized-rats
#8
JOURNAL ARTICLE
Reza Fartootzadeh, Ramezan Ali Taheri, Mohammad Reza Nourani, Kamelya Goudarzi
OBJECTIVES: Long-term potentiation (LTP) is a kind of synaptic plasticity and has a key role in learning and memory. Endocannabinoids and orexins are the endogenous systems that can modulate synaptic plasticity. Given that new studies have shown an interaction between cannabinoid and orexin systems in the brain, we decided to examine this interaction between the two systems on LTP induction in rat's hippocampus. MATERIALS AND METHODS: Twenty-eight male Wistar rats were used for evaluating the effects of co-administrating of cannabinoid-1 receptor (CB1R) antagonist (AM251) and orexin-2 receptor (OX2R) antagonist (TCS OX2 29) on the induction of LTP in the Schaffer collateral-CA1 synapses of rat hippocampus...
2024: Iranian Journal of Basic Medical Sciences
https://read.qxmd.com/read/38404644/-in-silico-analyses-of-the-involvement-of-gpr55-cb1r-and-trpv1-response-to-thc-contribution-to-temporal-lobe-epilepsy-structural-modeling-and-updated-evolution
#9
JOURNAL ARTICLE
Amy L Cherry, Michael J Wheeler, Karolina Mathisova, Mathieu Di Miceli
INTRODUCTION: The endocannabinoid (eCB) system is named after the discovery that endogenous cannabinoids bind to the same receptors as the phytochemical compounds found in Cannabis. While endogenous cannabinoids include anandamide (AEA) and 2-arachidonoylglycerol (2-AG), exogenous phytocannabinoids include Δ-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). These compounds finely tune neurotransmission following synapse activation, via retrograde signaling that activates cannabinoid receptor 1 (CB1R) and/or transient receptor potential cation channel subfamily V member 1 (TRPV1)...
2024: Frontiers in Neuroinformatics
https://read.qxmd.com/read/38402238/t-dope-probes-reveal-sensitivity-of-hippocampal-oscillations-to-cannabinoids-in-behaving-mice
#10
JOURNAL ARTICLE
Jongwoon Kim, Hengji Huang, Earl T Gilbert, Kaiser C Arndt, Daniel Fine English, Xiaoting Jia
Understanding the neural basis of behavior requires monitoring and manipulating combinations of physiological elements and their interactions in behaving animals. We developed a thermal tapering process enabling fabrication of low-cost, flexible probes combining ultrafine features: dense electrodes, optical waveguides, and microfluidic channels. Furthermore, we developed a semi-automated backend connection allowing scalable assembly. We demonstrate T-DOpE (Tapered Drug delivery, Optical stimulation, and Electrophysiology) probes achieve in single neuron-scale devices (1) high-fidelity electrophysiological recording (2) focal drug delivery and (3) optical stimulation...
February 24, 2024: Nature Communications
https://read.qxmd.com/read/38385841/therapeutic-like-activity-of-cannabidiolic-acid-methyl-ester-in-the-mk-801-mouse-model-of-schizophrenia-role-for-cannabinoid-cb1-and-serotonin-1a-receptors
#11
JOURNAL ARTICLE
Brandon Richardson, Courtney Clarke, Jacqueline Blundell, Francis R Bambico
Schizophrenia is a psychotic disorder with an increasing prevalence and incidence over the last two decades. The condition presents with a diverse array of positive, negative, and cognitive impairments. Conventional treatments often yield unsatisfactory outcomes, especially with negative symptoms. We investigated the role of prefrontocortical (PFC) N-methyl-D-aspartate receptors (NMDARs) in the pathophysiology and development of schizophrenia. We explored the potential therapeutic effects of cannabidiolic acid (CBDA) methyl ester (HU-580), an analogue of CBDA known to act as an agonist of the serotonin-1A receptor (5-HT1AR) and an antagonist of cannabinoid type 1 receptor (CB1R)...
February 22, 2024: European Journal of Neuroscience
https://read.qxmd.com/read/38380735/differential-cannabinoid-like-effects-and-pharmacokinetics-of-adb-bica-adb-binaca-adb-4en-pinaca-and-mdmb-4en-pinaca-in-mice-a-comparative-study
#12
JOURNAL ARTICLE
Fenghua Zhou, Xiaoli Wang, Sujun Tan, Yan Shi, Bing Xie, Ping Xiang, Bin Cong, Chunling Ma, Di Wen
Despite synthetic cannabinoids' (SCs) prevalent use among humans, these substances often lack comprehensive pharmacological data, primarily due to their rapid emergence in the market. This study aimed to discern differences and causal factors among four SCs (ADB-BICA, ADB-BINACA, ADB-4en-PINACA and MDMB-4en-PINACA), with respect to locomotor activity, body temperature and nociception threshold. Adult male C57BL/6 mice received intraperitoneal injections of varying doses (0.5, 0.1 and 0.02 mg/kg) of these compounds...
February 2024: Addiction Biology
https://read.qxmd.com/read/38336844/endogenous-cannabinoids-in-the-piriform-cortex-tune-olfactory-perception
#13
JOURNAL ARTICLE
Geoffrey Terral, Evan Harrell, Gabriel Lepousez, Yohan Wards, Dinghuang Huang, Tiphaine Dolique, Giulio Casali, Antoine Nissant, Pierre-Marie Lledo, Guillaume Ferreira, Giovanni Marsicano, Lisa Roux
Sensory perception depends on interactions between external inputs transduced by peripheral sensory organs and internal network dynamics generated by central neuronal circuits. In the sensory cortex, desynchronized network states associate with high signal-to-noise ratio stimulus-evoked responses and heightened perception. Cannabinoid-type-1-receptors (CB1Rs) - which influence network coordination in the hippocampus - are present in anterior piriform cortex (aPC), a sensory paleocortex supporting olfactory perception...
February 9, 2024: Nature Communications
https://read.qxmd.com/read/38328157/large-library-docking-for-cannabinoid-1-receptor-agonists-with-reduced-side-effects
#14
Tia A Tummino, Christos Iliopoulos-Tsoutsouvas, Joao M Braz, Evan S O'Brien, Reed M Stein, Veronica Craik, Ngan K Tran, Suthakar Ganapathy, Fangyu Liu, Yuki Shiimura, Fei Tong, Thanh C Ho, Dmytro S Radchenko, Yurii S Moroz, Sian Rodriguez Rosado, Karnika Bhardwaj, Jorge Benitez, Yongfeng Liu, Herthana Kandasamy, Claire Normand, Meriem Semache, Laurent Sabbagh, Isabella Glenn, John J Irwin, Kaavya Krishna Kumar, Alexandros Makriyannis, Allan I Basbaum, Brian K Shoichet
Large library docking can reveal unexpected chemotypes that complement the structures of biological targets. Seeking new agonists for the cannabinoid-1 receptor (CB1R), we docked 74 million tangible molecules, prioritizing 46 high ranking ones for de novo synthesis and testing. Nine were active by radioligand competition, a 20% hit-rate. Structure-based optimization of one of the most potent of these (K i = 0.7 µM) led to '4042 , a 1.9 nM ligand and a full CB1R agonist. A cryo-EM structure of the purified enantiomer of '4042 ( '1350 ) in complex with CB1R-G i1 confirmed its docked pose...
January 23, 2024: bioRxiv
https://read.qxmd.com/read/38318362/inhibition-of-cannabinoid-degradation-enhances-hippocampal-contextual-fear-memory-and-exhibits-anxiolytic-effects
#15
JOURNAL ARTICLE
Jinming Zhang, Junmin Zhang, Ruiqi Yuan, Wenxin Han, Yuan Chang, Lingyang Kong, Chunling Wei, Qiaohua Zheng, Xingchao Zhu, Zhiqiang Liu, Wei Ren, Jing Han
Recent studies have demonstrated the pivotal involvement of endocannabinoids in regulating learning and memory, but the conclusions obtained from different paradigms or contexts are somewhat controversial, and the underlying mechanisms remain largely elusive. Here, we show that JZL195, a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase, can enhance the performance of mice in a contextual fear conditioning task and increase the time spent in open arms in the elevated zero maze (EZM). Although the effect of JZL195 on fear memory could not be inhibited by antagonists of cannabinoid receptors, the effect on the EZM seems to be mediated by CB1R...
February 16, 2024: IScience
https://read.qxmd.com/read/38307967/anandamide-and-win-55212-2-afford-protection-in-rat-brain-mitochondria-in-a-toxic-model-induced-by-3-nitropropionic-acid-an-in-vitro-study
#16
JOURNAL ARTICLE
Marisol Maya-López, Luis Angel Monsalvo-Maraver, Ana Laura Delgado-Arzate, Carolina I Olivera-Pérez, Mohammed El-Hafidi, Alejandro Silva-Palacios, Omar Medina-Campos, José Pedraza-Chaverri, Michael Aschner, Alexey A Tinkov, Isaac Túnez, Socorro Retana-Márquez, Cecilia Zazueta, Abel Santamaría
Mitochondrial dysfunction plays a key role in the development of neurodegenerative disorders. In contrast, the regulation of the endocannabinoid system has been shown to promote neuroprotection in different neurotoxic paradigms. The existence of an active form of the cannabinoid receptor 1 (CB1R) in mitochondrial membranes (mitCB1R), which might exert its effects through the same signaling mechanisms as the cell membrane CB1R, has been shown to regulate mitochondrial activity. Although there is evidence suggesting that some cannabinoids may induce protective effects on isolated mitochondria, substantial evidence on the role of cannabinoids in mitochondria remains to be explored...
February 3, 2024: Molecular Neurobiology
https://read.qxmd.com/read/38293046/negative-allosteric-modulation-of-cb1-cannabinoid-receptor-signaling-decreases-intravenous-morphine-self-administration-and-relapse-in-mice
#17
Idaira Oliva, Fezaan Kazi, Lucas N Cantwell, Ganesh A Thakur, Jonathon D Crystal, Andrea G Hohmann
The endocannabinoid system interacts with the reward system to modulate responsiveness to natural reinforcers, as well as drugs of abuse. Previous preclinical studies suggested that direct blockade of CB1 cannabinoid receptors (CB1R) could be leveraged as a potential pharmacological approach to treat substance use disorder, but this strategy failed during clinical trials due to severe psychiatric side effects. Alternative strategies have emerged to circumvent the side effects of direct CB1 binding through the development of allosteric modulators...
January 19, 2024: bioRxiv
https://read.qxmd.com/read/38292517/fear-conditioning-and-extinction-distinctively-alter-bidirectional-synaptic-plasticity-within-the-amygdala-of-an-animal-model-of-post-traumatic-stress-disorder
#18
JOURNAL ARTICLE
Kwanghoon Park, Hoyong Park, ChiHye Chung
Synaptic plasticity in the amygdala plays an essential role in the formation and inhibition of fear memory; however, this plasticity has mainly been studied in the lateral amygdala, making it largely uninvestigated in other subnuclei. Here, we investigated long-term potentiation (LTP) and long-term depression (LTD) in the basolateral amygdala (BLA) to the medial division of the central amygdala (CEm) synapses of juvenile C57BL/6N (B6) and 129S1/SvImJ (S1) mice. We found that in naïve B6 and S1 mice, LTP was not induced at the BLA to CEm synapses, whereas fear conditioning lowered the threshold for LTP induction in these synapses of both B6 and S1 mice...
March 2024: Neurobiology of Stress
https://read.qxmd.com/read/38262742/-effects-of-repeated-treatment-with-the-monoacylglycerol-lipase-inhibitor-mjn110-on-pain-related-depression-of-nesting-and-cannabinoid-1-receptor-function-in-male-and-female-mice
#19
JOURNAL ARTICLE
Clare M Diester, Hallie Balint, James C Gillespie, Aron H Lichtman, Laura J Sim-Selley, Dana E Selley, S Stevens Negus
MJN110 inhibits the enzyme monoacylglycerol lipase (MAGL) to increase levels of the endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG), an endogenous high-efficacy agonist of cannabinoid 1 and 2 receptors (CB1/2 R). MAGL inhibitors are under consideration as candidate analgesics, and we reported previously that acute MJN110 produced partial antinociception in an assay of pain-related behavioral depression in mice. Given the need for repeated analgesic administration in many pain patients and the potential for analgesic tolerance during repeated treatment, this study examined antinociceptive effects of repeated MJN110 on pain-related behavioral depression and CB1R-mediated G-protein function...
January 23, 2024: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/38237793/macrophage-stimulating-protein-is-a-novel-transcriptional-target-of-estrogen-related-receptor-gamma-in-alcohol-intoxicated-mice
#20
JOURNAL ARTICLE
Yoon Seok Jung, Kamalakannan Radhakrishnan, Hyo-Jin Kim, Yong-Hoon Kim, Chul-Ho Lee, Hueng-Sik Choi
Macrophage stimulating protein (MSP) is a multifunctional serum protein produced in the liver, belonging to the plasminogen-related kringle protein family. It exerts diverse biological functions by activating a transmembrane receptor protein-tyrosine kinase known as RON in humans and SKT in mice. MSP plays a pivotal role in innate immunity and is involved in various activities such as cell survival, migration, and phagocytosis. Elucidating the regulatory mechanisms governing MSP gene expression is of great importance...
January 16, 2024: Cellular Signalling
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