{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:26:04Z","timestamp":1790735164337,"version":"4.1.0"},"reference-count":96,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIAAA-NIH grant AA027909, NIA-NIH"],"award-info":[{"award-number":["NIAAA-NIH grant AA027909, NIA-NIH"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>There are two well-characterized cannabinoid receptors (CB1R and CB2R and other candidates): the central nervous system (CNS) enriched CB1R and peripheral tissue enriched CB2R with a wide dynamic range of expression levels in different cell types of human tissues. Hepatocytes and neurons express low baseline CB1R and CB2R, respectively, and their cell-type-specific functions are not well defined. Here we report inducible expression of CB1R in the liver by high-fat and high sugar diet and CB2R in cortical neurons by methamphetamine. While there is less controversy about hepatocyte CB1R, the presence of functional neuronal CB2R is still debated to date. We found that neuron CB2R basal expression was higher than that of hepatocyte CB1R by measuring mRNA levels of specific isoform CB2A in neurons isolated by fluorescence-activated cell sorting (FACS) and CB1A in hepatocytes isolated by collagenase perfusion of liver. For in vivo studies, we generated hepatocyte, dopaminergic neuron, and microglia-specific conditional knockout mice (Abl-Cnr1\u0394, Dat-Cnr2\u0394, and Cx3cr1-Cnr2\u0394) of CB1R and CB2R by crossing Cnr1f\/f and Cnr2f\/f strains to Abl-Cre, Dat-Cre, and Cx3cr1-Cre deleter mouse strains, respectively. Our data reveals that neuron and microglia CB2Rs are involved in the \u201ctetrad\u201d effects of the mixed agonist WIN 55212-2, CB1R selective agonist arachidonyl-2\u2032-chloroethylamide (ACEA), and CB2R selective agonist JWH133. Dat-Cnr2\u0394 and Cx3cr1-Cnr2\u0394 mice showed genotypic differences in hypomobility, hypothermia, analgesia, and catalepsy induced by the synthetic cannabinoids. Alcohol conditioned place preference was abolished in DAT-Cnr2\u0394 mice and remained intact in Cx3cr1-Cnr2\u0394 mice in comparison to WT mice. These Cre-loxP recombinant mouse lines provide unique approaches in cannabinoid research for dissecting the complex endocannabinoid system that is implicated in many chronic disorders.<\/jats:p>","DOI":"10.3390\/ijms21249763","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T09:41:41Z","timestamp":1608543701000},"page":"9763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects"],"prefix":"10.3390","volume":"21","author":[{"given":"Qing-Rong","family":"Liu","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Canseco-Alba","sequence":"additional","affiliation":[{"name":"Department of Biology, William Paterson University, Wayne, NJ 07470, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6216-4743","authenticated-orcid":false,"given":"Ying","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1620-7204","authenticated-orcid":false,"given":"Hiroki","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry, Graduate School of Medical Science, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7561-8927","authenticated-orcid":false,"given":"Emmanuel S.","family":"Onaivi","sequence":"additional","affiliation":[{"name":"Department of Biology, William Paterson University, Wayne, NJ 07470, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,21]]},"reference":[{"key":"ref_1","first-page":"1046","article-title":"Pharmacology and stereoselectivity of structurally novel cannabinoids in mice","volume":"247","author":"Little","year":"1988","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17410","DOI":"10.1038\/s41598-017-17796-y","article-title":"Cannabinoid type 2 receptors in dopamine neurons inhibits psychomotor behaviors, alters anxiety, depression and alcohol preference","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41401-018-0152-1","article-title":"Identification of novel mouse and rat CB1R isoforms and in silico modeling of human CB1R for peripheral cannabinoid therapeutics","volume":"40","author":"Liu","year":"2019","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1038\/npp.2014.297","article-title":"Species differences in cannabinoid receptor 2 and receptor responses to cocaine self-administration in mice and rats","volume":"40","author":"Zhang","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/365061a0","article-title":"Molecular characterization of a peripheral receptor for cannabinoids","volume":"365","author":"Munro","year":"1993","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107477","DOI":"10.1016\/j.pharmthera.2020.107477","article-title":"The therapeutic potential of second and third generation CB1R antagonists","volume":"208","author":"Cinar","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1177\/0269881111400652","article-title":"CNS effects of CB2 cannabinoid receptors: Beyond neuro-immuno-cannabinoid activity","volume":"26","author":"Onaivi","year":"2012","journal-title":"J. Psychopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/j.1476-5381.2010.00729.x","article-title":"CB2: A cannabinoid receptor with an identity crisis","volume":"160","author":"Atwood","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/s41401-018-0037-3","article-title":"CB2 receptor antibody signal specificity: Correlations with the use of partial CB2-knockout mice and anti-rat CB2 receptor antibodies","volume":"40","author":"Zhang","year":"2019","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_10","first-page":"1620","article-title":"Cannabinoid inhibition of the processing of intact lysozyme by macrophages: Evidence for CB2 receptor participation","volume":"289","author":"McCoy","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0014-2999(99)00402-1","article-title":"Evaluation of the cannabinoid CB2 receptor-selective antagonist, SR144528: Further evidence for cannabinoid CB2 receptor absence in the rat central nervous system","volume":"377","author":"Griffin","year":"1999","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s12974-018-1174-9","article-title":"Cannabinoid CB2 receptors in the mouse brain: Relevance for Alzheimer\u2019s disease","volume":"15","author":"Lopez","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Schmole, A.C., Lundt, R., Gennequin, B., Schrage, H., Beins, E., Kramer, A., Zimmer, T., Limmer, A., Zimmer, A., and Otte, D.M. (2015). Expression Analysis of CB2-GFP BAC Transgenic Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145472"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1038\/npp.2012.22","article-title":"Decreased cocaine motor sensitization and self-administration in mice overexpressing cannabinoid CB(2) receptors","volume":"37","author":"Trigo","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.neuropharm.2019.02.004","article-title":"Increased expression of cannabinoid CB2 and serotonin 5-HT1A heteroreceptor complexes in a model of newborn hypoxic-ischemic brain damage","volume":"152","author":"Franco","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.neuropharm.2013.05.034","article-title":"Synaptic plasticity alterations associated with memory impairment induced by deletion of CB2 cannabinoid receptors","volume":"73","author":"Caltana","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1177\/0269881110367732","article-title":"Expression of the mRNA coding the cannabinoid receptor 2 in the pallidal complex of Macaca fascicularis","volume":"25","author":"Lanciego","year":"2011","journal-title":"J. Psychopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.pbb.2019.06.007","article-title":"Alcohol-induced conditioned place preference is modulated by CB2 cannabinoid receptors and modifies levels of endocannabinoids in the mesocorticolimbic system","volume":"183","author":"Warnault","year":"2019","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-21737-2_1","article-title":"Endocannabinoid System Components: Overview and Tissue Distribution","volume":"1162","author":"Joshi","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5780","DOI":"10.1073\/pnas.96.10.5780","article-title":"Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice","volume":"96","author":"Zimmer","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0014-2999(00)00211-9","article-title":"Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB(2) receptor","volume":"396","author":"Buckley","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1007\/s00125-010-1894-6","article-title":"Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age","volume":"53","author":"Agudo","year":"2010","journal-title":"Diabetologia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1002\/oby.22403","article-title":"Diet-Induced Obesity in Cannabinoid-2 Receptor Knockout Mice and Cannabinoid Receptor 1\/2 Double-Knockout Mice","volume":"27","author":"Alshaarawy","year":"2019","journal-title":"Obesity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.1088208","article-title":"CB1 cannabinoid receptors and on-demand defense against excitotoxicity","volume":"302","author":"Marsicano","year":"2003","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1538\/expanim.55.137","article-title":"High-efficiency CAG-FLPe deleter mice in C57BL\/6J background","volume":"55","author":"Kanki","year":"2006","journal-title":"Exp. Anim."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6191","DOI":"10.1073\/pnas.93.12.6191","article-title":"Flp recombinase promotes site-specific DNA recombination in embryonic stem cells and transgenic mice","volume":"93","author":"Dymecki","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/(SICI)1526-968X(200002)26:2<99::AID-GENE1>3.0.CO;2-B","article-title":"Cre recombinase: The universal reagent for genome tailoring","volume":"26","author":"Nagy","year":"2000","journal-title":"Genesis"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.neuropharm.2014.01.007","article-title":"Pre- and postsynaptic type-1 cannabinoid receptors control the alterations of glutamate transmission in experimental autoimmune encephalomyelitis","volume":"79","author":"Musella","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.neuron.2006.07.006","article-title":"The endocannabinoid system controls key epileptogenic circuits in the hippocampus","volume":"51","author":"Monory","year":"2006","journal-title":"Neuron"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.bone.2017.12.018","article-title":"Age-related regulation of bone formation by the sympathetic cannabinoid CB1 receptor","volume":"108","author":"Deis","year":"2018","journal-title":"Bone"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/nn1916","article-title":"Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors","volume":"10","author":"Agarwal","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1002\/glia.23314","article-title":"Localization of the cannabinoid type-1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus","volume":"66","author":"Puente","year":"2018","journal-title":"Glia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.cell.2012.01.037","article-title":"Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD","volume":"148","author":"Han","year":"2012","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4148","DOI":"10.1172\/JCI83626","article-title":"Adipocyte cannabinoid receptor CB1 regulates energy homeostasis and alternatively activated macrophages","volume":"127","author":"Mancini","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/dom.13150","article-title":"Cannabinoid-1 receptor deletion in podocytes mitigates both glomerular and tubular dysfunction in a mouse model of diabetic nephropathy","volume":"20","author":"Jourdan","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.4049\/jimmunol.1201777","article-title":"Cannabinoid 1 receptors in keratinocytes modulate proinflammatory chemokine secretion and attenuate contact allergic inflammation","volume":"190","author":"Gaffal","year":"2013","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1172\/JCI34827","article-title":"Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice","volume":"118","author":"Liu","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.neuron.2016.03.034","article-title":"Cannabinoid Type 2 Receptors Mediate a Cell Type-Specific Plasticity in the Hippocampus","volume":"90","author":"Stempel","year":"2016","journal-title":"Neuron"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.neuropharm.2018.07.020","article-title":"Cannabinoid type 2 receptors mediate a cell type-specific self-inhibition in cortical neurons","volume":"139","author":"Stumpf","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.7554\/eLife.55582","article-title":"Protective role of neuronal and lymphoid cannabinoid CB2 receptors in neuropathic pain","volume":"9","author":"Cabanero","year":"2020","journal-title":"Elife"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.tips.2006.11.001","article-title":"Cannabinoid CB2 receptor: A new target for controlling neural cell survival?","volume":"28","author":"Romero","year":"2007","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1038\/s41598-020-59827-1","article-title":"Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans","volume":"10","author":"Hu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1080\/17843286.2018.1461754","article-title":"Cannabinoid receptor 2: A potential novel therapeutic target for sepsis?","volume":"74","author":"He","year":"2019","journal-title":"Acta Clin. Belg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.1007\/s00018-016-2300-4","article-title":"The CB2 receptor and its role as a regulator of inflammation","volume":"73","author":"Turcotte","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"13958","DOI":"10.1038\/ncomms13958","article-title":"Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity","volume":"8","author":"Soethoudt","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"926","DOI":"10.2337\/db09-1482","article-title":"CB1 antagonism exerts specific molecular effects on visceral and subcutaneous fat and reverses liver steatosis in diet-induced obese mice","volume":"59","author":"Jourdan","year":"2010","journal-title":"Diabetes"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.neuron.2017.06.020","article-title":"Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia Microglia","volume":"95","author":"Schuebel","year":"2017","journal-title":"Neuron"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/jnc.12381","article-title":"Detection of molecular alterations in methamphetamine-activated Fos-expressing neurons from a single rat dorsal striatum using fluorescence-activated cell sorting (FACS)","volume":"128","author":"Liu","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_49","first-page":"e3061","article-title":"Behavioral Evaluation of Seeking and Preference of Alcohol in Mice Subjected to Stress","volume":"8","author":"Schanz","year":"2018","journal-title":"Bio. Protoc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1053\/j.gastro.2012.01.032","article-title":"Hepatic cannabinoid receptor-1 mediates diet-induced insulin resistance via inhibition of insulin signaling and clearance in mice","volume":"142","author":"Liu","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1111\/j.1478-3231.2010.02298.x","article-title":"Cannabinoid receptor 1 and 2 agonists increase lipid accumulation in hepatocytes","volume":"30","author":"Spahr","year":"2010","journal-title":"Liver Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1038\/s41401-019-0213-0","article-title":"Protective effects of specific cannabinoid receptor 2 agonist GW405833 on concanavalin A-induced acute liver injury in mice","volume":"40","author":"Huang","year":"2019","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/psc.2474","article-title":"Critique of the use of fluorescence-based reporters in Escherichia coli as a screening tool for the identification of peptide inhibitors of Abeta42 aggregation","volume":"19","author":"Wright","year":"2013","journal-title":"J. Pept. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4018","DOI":"10.1038\/s41598-018-22330-9","article-title":"Changes in global translation elongation or initiation rates shape the proteome via the Kozak sequence","volume":"8","author":"Acevedo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.neuropharm.2018.08.007","article-title":"Revisiting cannabinoid receptor 2 expression and function in murine retina","volume":"141","author":"Murataeva","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Zhang, Y., and Stefanovic, B. (2016). LARP6 Meets Collagen mRNA: Specific Regulation of Type I Collagen Expression. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17030419"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Moreno-Garcia, A., Bernal-Chico, A., Colomer, T., Rodriguez-Antiguedad, A., Matute, C., and Mato, S. (2020). Gene Expression Analysis of Astrocyte and Microglia Endocannabinoid Signaling during Autoimmune Demyelination. Biomolecules, 10.","DOI":"10.3390\/biom10091228"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1189\/jlb.1012523","article-title":"Attenuation of HIV-1 replication in macrophages by cannabinoid receptor 2 agonists","volume":"93","author":"Ramirez","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1111\/adb.12367","article-title":"Expression of functional cannabinoid CB2 receptor in VTA dopamine neurons in rats","volume":"22","author":"Zhang","year":"2017","journal-title":"Addict. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.bbi.2017.10.021","article-title":"Selective activation of cannabinoid receptor-2 reduces neuroinflammation after traumatic brain injury via alternative macrophage polarization","volume":"68","author":"Braun","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.eplepsyres.2018.10.002","article-title":"The spatiotemporal expression changes of CB2R in the hippocampus of rats following pilocarpine-induced status epilepticus","volume":"148","author":"Wu","year":"2018","journal-title":"Epilepsy Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Yu, S.J., Reiner, D., Shen, H., Wu, K.J., Liu, Q.R., and Wang, Y. (2015). Time-Dependent Protection of CB2 Receptor Agonist in Stroke. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132487"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jchemneu.2017.07.007","article-title":"Receptor visualization and the atomic bomb. A historical account of the development of the chemical neuroanatomy of receptors for neurotransmitters and drugs during the Cold War","volume":"88","author":"Palacios","year":"2018","journal-title":"J. Chem. Neuroanat."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jchemneu.2015.12.016","article-title":"Multiplexed neurochemical signaling by neurons of the ventral tegmental area","volume":"73","author":"Barker","year":"2016","journal-title":"J. Chem. Neuroanat."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ye, A.Y., Liu, Q.R., Li, C.Y., Zhao, M., and Qu, H. (2014). Human transporter database: Comprehensive knowledge and discovery tools in the human transporter genes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088883"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/nn.2874","article-title":"Brain cannabinoid CB2 receptors modulate cocaine\u2019s actions in mice","volume":"14","author":"Xi","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ebiom.2019.03.040","article-title":"Mechanisms of cannabinoid CB2 receptor-mediated reduction of dopamine neuronal excitability in mouse ventral tegmental area","volume":"42","author":"Ma","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0890-8508(91)90033-G","article-title":"Strand-specific detection of enteroviral RNA in myocardial tissue by in situ hybridization","volume":"5","author":"Hohenadl","year":"1991","journal-title":"Mol. Cell. Probes"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ab.2006.02.013","article-title":"A multiplex branched DNA assay for parallel quantitative gene expression profiling","volume":"352","author":"Flagella","year":"2006","journal-title":"Anal. Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.1007\/s00429-014-0823-8","article-title":"Detection of cannabinoid receptors CB1 and CB2 within basal ganglia output neurons in macaques: Changes following experimental parkinsonism","volume":"220","author":"Sierra","year":"2015","journal-title":"Brain Struct. Funct."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.celrep.2014.12.005","article-title":"Input- and cell-type-specific endocannabinoid-dependent LTD in the striatum","volume":"10","author":"Wu","year":"2015","journal-title":"Cell Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/sj.bjp.0705726","article-title":"Endocannabinoid-mediated short-term synaptic plasticity: Depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE)","volume":"142","author":"Diana","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13195-019-0475-2","article-title":"Neurexin 3 transmembrane and soluble isoform expression and splicing haplotype are associated with neuron inflammasome and Alzheimer\u2019s disease","volume":"11","author":"Hishimoto","year":"2019","journal-title":"Alzheimers Res. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Duff, G., Argaw, A., Cecyre, B., Cherif, H., Tea, N., Zabouri, N., Casanova, C., Ptito, M., and Bouchard, J.F. (2013). Cannabinoid receptor CB2 modulates axon guidance. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070849"},{"key":"ref_75","first-page":"475","article-title":"CB2R orchestrates neuronal autophagy through regulation of the mTOR signaling pathway in the hippocampus of developing rats with status epilepticus","volume":"45","author":"Wu","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1006\/bbrc.1996.1358","article-title":"Cloning of the human sodium lodide symporter","volume":"226","author":"Smanik","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/78630","article-title":"The mammary gland iodide transporter is expressed during lactation and in breast cancer","volume":"6","author":"Tazebay","year":"2000","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1007\/s00125-018-4576-4","article-title":"Absence of cannabinoid 1 receptor in beta cells protects against high-fat\/high-sugar diet-induced beta cell dysfunction and inflammation in murine islets","volume":"61","author":"Montoro","year":"2018","journal-title":"Diabetologia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5850","DOI":"10.1096\/fj.201801145R","article-title":"Muscle cannabinoid 1 receptor regulates Il-6 and myostatin expression, governing physical performance and whole-body metabolism","volume":"33","author":"Montoro","year":"2019","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/dvg.20228","article-title":"Characterization of a mouse strain expressing Cre recombinase from the 3\u2019 untranslated region of the dopamine transporter locus","volume":"44","author":"Backman","year":"2006","journal-title":"Genesis"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.bbr.2018.11.043","article-title":"Behavioral effects of psychostimulants in mutant mice with cell-type specific deletion of CB2 cannabinoid receptors in dopamine neurons","volume":"360","author":"Schanz","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.neuron.2017.04.011","article-title":"Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins","volume":"94","author":"Chen","year":"2017","journal-title":"Neuron"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4774","DOI":"10.1523\/JNEUROSCI.0360-18.2018","article-title":"Genetic Ablation of All Cerebellins Reveals Synapse Organizer Functions in Multiple Regions Throughout the Brain","volume":"38","author":"Seigneur","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_84","first-page":"e57270","article-title":"Stereotaxic Surgery for Genetic Manipulation in Striatal Cells of Neonatal Mouse Brains","volume":"137","author":"Chen","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.molmet.2017.01.001","article-title":"Cholinergic neurons in the dorsomedial hypothalamus regulate food intake","volume":"6","author":"Jeong","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3389\/fncel.2020.00145","article-title":"A Whole-Brain Cell-Type-Specific Sparse Neuron Labeling Method and Its Application in a Shank3 Autistic Mouse Model","volume":"14","author":"Chen","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ibror.2019.11.006","article-title":"Targeted viral vector transduction of relaxin-3 neurons in the rat nucleus incertus using a novel cell-type specific promoter","volume":"8","author":"Wykes","year":"2020","journal-title":"IBRO Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"FSO625","DOI":"10.2144\/fsoa-2020-0124","article-title":"Cannabis for COVID-19: Can cannabinoids quell the cytokine storm?","volume":"6","author":"Onaivi","year":"2020","journal-title":"Future Sci. OA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1126\/science.abd3255","article-title":"Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein","volume":"370","author":"Toelzer","year":"2020","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1096\/fj.00-0291rev","article-title":"Transgenic study of energy homeostasis equation: Implications and confounding influences","volume":"14","author":"Inui","year":"2000","journal-title":"FASEB J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/nn.3053","article-title":"Mitochondrial CB(1) receptors regulate neuronal energy metabolism","volume":"15","author":"Benard","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.brainresbull.2020.03.014","article-title":"Age-dependent Alteration in Mitochondrial Dynamics and Autophagy in Hippocampal Neuron of Cannabinoid CB1 Receptor-deficient Mice","volume":"160","author":"Kataoka","year":"2020","journal-title":"Brain Res. Bull."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12986-019-0377-0","article-title":"Dietary curcumin enhances insulin clearance in diet-induced obese mice via regulation of hepatic PI3K-AKT axis and IDE, and preservation of islet integrity","volume":"16","author":"Kim","year":"2019","journal-title":"Nutr. Metab"},{"key":"ref_94","first-page":"e58323","article-title":"Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method","volume":"140","author":"Salem","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_95","first-page":"e54358","article-title":"Fluorescence Activated Cell Sorting (FACS) and Gene Expression Analysis of Fos-expressing Neurons from Fresh and Frozen Rat Brain Tissue","volume":"114","author":"Rubio","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nature05453","article-title":"Genome-wide atlas of gene expression in the adult mouse brain","volume":"445","author":"Lein","year":"2007","journal-title":"Nature"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9763\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:47:56Z","timestamp":1760179676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,21]]},"references-count":96,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21249763"],"URL":"https:\/\/doi.org\/10.3390\/ijms21249763","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,21]]}}}