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Fabrício de Araújo Moreirahttp://lattes.cnpq.br/9762674962145732Cleiton Lopes AguiarFabíola Mara Ribeirohttp://lattes.cnpq.br/1963466236276683Jadna Bogado Lopes2021-04-12T15:56:07Z2021-04-12T15:56:07Z2017-08-16http://hdl.handle.net/1843/35647As drogas de abuso, a exemplo da cocaína, exercem efeito recompensador e facilitam a neurotransmissão dopaminérgica na via mesolímbica. O sistema endocanabinoide, representado por receptores canabinoides (CB1 e CB2), endocanabinoides e as enzimas que os sintetizam e degradam, modula esta via de neurotransmissão e pode ser um importante alvo de terapias farmacológicas para o tratamento do transtorno por uso de substância. Neste trabalho, testamos a hipótese de que receptores canabinoides estão evolvidos nos efeitos de sensibilização motora, preferência condicionada ao lugar (PCL) e ativação de neurônios hipocampais induzidas por cocaína. Para tal, camundongos Swiss receberam injeções de AM251 (antagonista de receptor CB1) ou JWH133 (agonista de receptor CB2) durante as fases de aquisição ou expressão dos comportamentos citados. O AM251 inibiu a sensibilização, quando administrado nas fases de aquisição (0,3, 1 e 3 mg/kg) ou expressão (1 e 3 mg/kg), e a PCL, quando administrado na fase de aquisição (10 mg/kg). O JWH133 não impediu o efeito agudo da cocaína. Porém, atenuou a sensibilização quando administrado nas fases de aquisição (0,3 e 1 mg/kg) ou expressão (1 e 3 mg/kg). Além disso, a administração de JWH133 (10 mg/kg) preveniu a PCL por cocaína em ambas as fases. Os efeitos do JWH133 foram revertidos com a administração de AM630 (antagonista de receptores CB2). A atenuação da memória contextual induzida por cocaína foi acompanhada por diminuição na ativação neuronial (células positivas para c-Fos) no hipocampo dos animais tratados com AM251 e JWH133. Assim, os efeitos comportamentais e celulares induzidos por cocaína parecem ser mediados pela ativação do receptor CB1 e inibidos pela ativação do receptor CB2. Considerando que ambos receptores são acoplados à proteína Gi/o, especulamos que estes receptores atuem em tipos distintos de neurônios, estando CB1 e CB2 localizados em neurônios GABAérgicos e dopaminérgicos, respectivamente.Drugs of abuse, such as cocaine, induce a reward effect and facilitate dopaminergic neurotransmission on the mesolimbic pathway. The endocannabinoid system, represented by cannabinoid receptors (CB1 e CB2), endocannabinoids and enzymes responsible for their synthesis and degradation, modulates the neurotransmission pathway and can be an important pharmacological target for the treatment of addiction. Herein, we tested the hypothesis that cannabinoid receptors are implicated on motor sensitization effects, conditioned place preference (CPP) and hippocampal neuronial activation induced by cocaine. Swiss male mice received AM251 (CB1 receptor antagonist) or JWH133 (CB2 receptor agonist) injections during acquisition or expression phases of the above mentioned behavioural tasks. AM251 inhibited sensitization, when administered during the acquisition (0,3, 1 and 3 mg/kg) or expression. (1 and 3 mg/kg) phases, and CPP, when administered during acquisition phase (10 mg/kg). JWH133 did not prevent the acute cocaine-effect. However, it attenuated sensitization when administered during acquisition (0,3 and 1 mg/kg) or expression (1 and 3 mg/kg) phases. Moreover, administration of JWH133 (10 mg/kg) prevented cocaine-induced CPP on both phases. JWH133 effects were reverted by AM630 (CB2 receptor antagonist) administration. The attenuation of the cocaine-induced contextual memory occurred along with a decrease on neuronal activation (c-Fos positive cells) on the hippocampus of animals treated with AM251 and JWH133. Therefore, behavioural and cellular effects induced by cocaine seem to be mediated by activation of CB1 receptor and inhibited by activation of CB2 receptor. As both receptors are Gi/o coupled receptors, we speculate that they act on different neuronal types, with CB1 e CB2 localized on GABAergic and dopaminergic neurons, respectively.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Ciências Biológicas - Fisiologia e FarmacologiaUFMGBrasilICB - INSTITUTO DE CIÊNCIAS BIOLOGICAShttp://creativecommons.org/licenses/by-nc-nd/3.0/pt/info:eu-repo/semantics/openAccessReceptor CB1 de canabinoideReceptor CB2 de canabinoideMemóriaCB1CB2PsicoestimulanteMemóriaRecompensaEnvolvimento de receptores canabinoides na sensibilização e preferência condicionada ao lugar induzidas por cocaínainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINAL2017 DISSERTAÇÃO_IMPRESSÃO_JADNA_versão final.pdf2017 DISSERTAÇÃO_IMPRESSÃO_JADNA_versão final.pdfapplication/pdf1471502https://repositorio.ufmg.br/bitstream/1843/35647/1/2017%20DISSERTA%c3%87%c3%83O_IMPRESS%c3%83O_JADNA_vers%c3%a3o%20final.pdf8e5e449944058e758253df2c85e10861MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.ufmg.br/bitstream/1843/35647/2/license_rdfcfd6801dba008cb6adbd9838b81582abMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82119https://repositorio.ufmg.br/bitstream/1843/35647/3/license.txt34badce4be7e31e3adb4575ae96af679MD531843/356472021-04-12 12:56:07.465oai:repositorio.ufmg.br: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Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2021-04-12T15:56:07Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
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