Endogenous cannabinoids induce fever through the activation of CB1 receptors

dc.creatorFraga, D
dc.creatorZanoni, CIS
dc.creatorRae, GA
dc.creatorParada, CA
dc.creatorSouza, GEP
dc.date2009
dc.dateAUG
dc.date2014-11-20T08:11:31Z
dc.date2015-11-26T16:30:17Z
dc.date2014-11-20T08:11:31Z
dc.date2015-11-26T16:30:17Z
dc.date.accessioned2018-03-28T23:11:20Z
dc.date.available2018-03-28T23:11:20Z
dc.identifierBritish Journal Of Pharmacology. Wiley-blackwell, v. 157, n. 8, n. 1494, n. 1501, 2009.
dc.identifier0007-1188
dc.identifierWOS:000268531100019
dc.identifier10.1111/j.1476-5381.2009.00312.x
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/64747
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/64747
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/64747
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1269938
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionBackground and purpose: The effects of centrally administered cannabinoids on body core temperature (Tc) and the contribution of endogenous cannabinoids to thermoregulation and fever induced by lipopolysaccharide (LPS) (Sigma Chem. Co., St. Louis, MO, USA) were investigated. Experimental approach: Drug-induced changes in Tc of male Wistar rats were recorded over 6 h using a thermistor probe (Yellow Springs Instruments 402, Dayton, OH, USA) inserted into the rectum. Key results: Injection of anandamide [(arachidonoylethanolamide (AEA); Tocris, Ellisville, MO, USA], 0.01-1 mu g i.c.v. or 0.1-100 ng intra-hypothalamic (i.h.), induced graded increases in Tc (peaks 1.5 and 1.6 degrees C at 4 h after 1 mu g i.c.v. or 10 ng i.h.). The effect of AEA (1 mu g, i.c.v.) was preceded by decreases in tail skin temperature and heat loss index (values at 1.5 h: vehicle 0.62, AEA 0.48). Bell-shaped curves were obtained for the increase in Tc induced by the fatty acid amide hydrolase inhibitor [3-(3-carbamoylphenyl)phenyl] N-cyclohexylcarbamate (Cayman Chemical Co., Ann Arbor, MI, USA) (0.001-1 ng i.c.v.; peak 1.9 degrees C at 5 h after 0.1 ng) and arachidonyl-2-chloroethylamide (ACEA; Tocris) (selective CB1 agonist; 0.001-1 mu g i.c.v.; peak 1.4 degrees C 5 h after 0.01 mu g), but (R,S)-(+)-(2-Iodo-5-nitrobenzoyl)-[1-(1-methyl-piperidin-2-ylmethyl)-1H-indole-3-yl] methanone (Tocris) (selective CB2 agonist) had no effect on Tc. AEA-induced fever was unaffected by i.c.v. pretreatment with 6-Iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indole-3-yl](4-methoxyphenyl) methanone (Tocris) (selective CB2 antagonist), but reduced by i.c.v. pretreatment with N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251; Tocris) (selective CB1 antagonist). AM251 also reduced the fever induced by ACEA or LPS. Conclusions and implications: The endogenous cannabinoid AEA induces an integrated febrile response through activation of CB1 receptors. Endocannabinoids participate in the development of the febrile response to LPS constituting a target for antipyretic therapy.
dc.description157
dc.description8
dc.description1494
dc.description1501
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundacao de Amparo a Pesquisa de Sao Paulo [2007/04791-1]
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionCNPq [304627/2007-0]
dc.descriptionFundacao de Amparo a Pesquisa de Sao Paulo [2007/04791-1]
dc.languageen
dc.publisherWiley-blackwell
dc.publisherMalden
dc.publisherEUA
dc.relationBritish Journal Of Pharmacology
dc.relationBr. J. Pharmacol.
dc.rightsfechado
dc.rightshttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.sourceWeb of Science
dc.subjectanandamide
dc.subjectACEA
dc.subjectAM251
dc.subjectAM630
dc.subjectAM1241
dc.subjectURB597
dc.subjectcapsazepine
dc.subjectfever
dc.subjectLPS
dc.subjectPreoptic-anterior Hypothalamus
dc.subjectBody-temperature
dc.subjectMolecular Characterization
dc.subjectFunctional Expression
dc.subjectPorcine Brain
dc.subjectAnandamide
dc.subjectRat
dc.subjectDelta-9-tetrahydrocannabinol
dc.subjectThermoregulation
dc.subjectInterleukin-6
dc.titleEndogenous cannabinoids induce fever through the activation of CB1 receptors
dc.typeArtículos de revistas


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