title: Anandamide reverses depressive-like behavior, neurochemical abnormalities and oxidative-stress parameters in streptozotocin-diabetic rats: Role of CB1 receptors.
abstract: The pathophysiology associated with increased prevalence of depression in diabetics is not completely understood, although studies have pointed the endocannabinoid system as a possible target. Then, we aimed to investigate the role of this system in the pathophysiology of depression associated with diabetes. For this, diabetic (DBT) male Wistar rats were intraperitoneally treated with cannabinoid CB1 (AM251, 1mg/kg) or CB2 (AM630, 1mg/kg) receptor antagonists followed by anandamide (AEA, 0.005mg/kg) and then submitted to the forced swimming test (FST). Oxidative stress parameters, CB1 receptor expression and serotonin (5-HT) and noradrenaline levels in the hippocampus (HIP) and prefrontal cortex (PFC) were also performed. It was observed that DBT animals presented a more pronounced depressive-like behavior and increase of CB1 receptor expression in the HIP. AEA treatment induced a significant improvement in the depressive-like behavior, which was reversed by the CB1 antagonist AM251, without affecting the hyperglycemia or weight gain. AEA was also able to restore the elevated CB1 expression and also to elevate the reduced level of 5-HT in the HIP from DBT animals. In addition, AEA restored the elevated noradrenaline levels in the PFC and induced a neuroprotective effect by restoring the decreased reduced glutathione and increased lipid hydroperoxides levels along with the decreased superoxide dismutase activity observed in HIP or PFC. Together, our data suggest that in depression associated with diabetes, the endocannabinoid anandamide has a potential to induce neuroadaptative changes able to improve the depressive-like response by its action as a CB1 receptor agonist.
authors.affiliation: Department of Pharmacology, Biological Sciences Building, Federal University of Paraná, Coronel Francisco H dos Santos S/N, P.O. Box 19031, Curitiba, PR 81540-990, Brazil.
authors.forename: Helen
authors.initials: H
authors.lastname: de Morais
authors.affiliation: Department of Pharmacology, Biological Sciences Building, Federal University of Paraná, Coronel Francisco H dos Santos S/N, P.O. Box 19031, Curitiba, PR 81540-990, Brazil.
authors.forename: Camila P
authors.initials: CP
authors.lastname: de Souza
authors.affiliation: Department of Pharmacology, Biological Sciences Building, Federal University of Paraná, Coronel Francisco H dos Santos S/N, P.O. Box 19031, Curitiba, PR 81540-990, Brazil.
authors.forename: Luisa M
authors.initials: LM
authors.lastname: da Silva
authors.affiliation: Department of Pharmacology, Biological Sciences Building, Federal University of Paraná, Coronel Francisco H dos Santos S/N, P.O. Box 19031, Curitiba, PR 81540-990, Brazil.
authors.forename: Daniele M
authors.initials: DM
authors.lastname: Ferreira
authors.affiliation: Department of Pharmacology, Biological Sciences Building, Federal University of Paraná, Coronel Francisco H dos Santos S/N, P.O. Box 19031, Curitiba, PR 81540-990, Brazil.
authors.forename: Cristiane Hatsuko
authors.initials: CH
authors.lastname: Baggio
authors.affiliation: Department of Pharmacology, Division of Biological Sciences, Federal University of Santa Catarina, Florianopólis, SC, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Vanvossen
authors.affiliation: Institute of Neurosciences and Behavior (INeC) and Laboratory of Neuropsychopharmacology of Faculty of Philosophy, Sciences and Letters of University of São Paulo, Ribeirão Preto, SP 14040-901, Brazil.
authors.forename: Milene
authors.initials: M
authors.lastname: Cristina de Carvalho
authors.affiliation: Department of Pharmacology, Division of Biological Sciences, Federal University of Santa Catarina, Florianopólis, SC, Brazil.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: da Silva-Santos
authors.affiliation: Department of Pharmacology, Division of Biological Sciences, Federal University of Santa Catarina, Florianopólis, SC, Brazil.
authors.forename: Leandro José
authors.initials: LJ
authors.lastname: Bertoglio
authors.affiliation: Department of Pharmacology, Biological Sciences Building, Federal University of Paraná, Coronel Francisco H dos Santos S/N, P.O. Box 19031, Curitiba, PR 81540-990, Brazil.
authors.forename: Joice M
authors.initials: JM
authors.lastname: Cunha
authors.affiliation: Department of Pharmacology, Biological Sciences Building, Federal University of Paraná, Coronel Francisco H dos Santos S/N, P.O. Box 19031, Curitiba, PR 81540-990, Brazil. Electronic address: janaina.zanoveli@ufpr.br.
authors.forename: Janaina M
authors.initials: JM
authors.lastname: Zanoveli
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology*; D003921:Diabetes Mellitus, Experimental / Q000523:psychology*; D063388:Endocannabinoids / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013550:Swimming / Q000523:psychology
chemical_list: D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D063388:Endocannabinoids; D007211:Indoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D012701:Serotonin; C103505:AM 251; C094023:iodopravadoline; C078814:anandamide; D009638:Norepinephrine
keywords: CB1 receptor; Depression; Diabetes; Noradrenaline; Oxidative stress; Serotonin