title: Preclinical Evidences for an Antimanic Effect of Carvedilol.
abstract: Oxidative imbalance, alterations in brain-derived neurotrophic factor (BDNF), and mitochondrial dysfunction are implicated in bipolar disorder (BD) pathophysiology and comorbidities, for example, cardiovascular conditions. Carvedilol (CVD), a nonselective beta-blocker widely used for the treatment of hypertension, presents antioxidant and mitochondrial stabilizing properties. Thus, we hypothesized that CVD would prevent and/or reverse mania-like behavioral and neurochemical alterations induced by lisdexamfetamine dimesylate (LDX). To do this, male Wistar rats were submitted to two different protocols, namely, prevention and reversal. In the prevention treatment the rats received daily oral administration (mg/kg) of CVD (2.5, 5 or 7.5), saline, valproate (VAL200), or the combination of CVD5 + VAL100 for 7 days. From the 8th to 14th day LDX was added. In the reversal protocol LDX was administered for 7 days with the drugs being added from the 8th to 14th day of treatment. Two hours after the last administration the behavioral (open field and social interaction) and neurochemical (reduced glutathione, lipid peroxidation, and BDNF) determinations were performed. The results showed that CVD prevented and reversed the behavioral and neurochemical alterations induced by LDX. The administration of CVD5 + VAL100 potentiated the effect of VAL200 alone. Taken together these results demonstrate a possible antimanic effect of CVD in this preclinical model.
authors.affiliation: Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
authors.forename: Greicy Coelho
authors.initials: GC
authors.lastname: de Souza
authors.affiliation: Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
authors.forename: Julia Ariana de S
authors.initials: JA
authors.lastname: Gomes
authors.affiliation: Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
authors.forename: Ana Isabelle
authors.initials: AI
authors.lastname: de Góis Queiroz
authors.affiliation: Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
authors.forename: Maíra Morais
authors.initials: MM
authors.lastname: de Araújo
authors.affiliation: Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
authors.forename: Lígia Menezes
authors.initials: LM
authors.lastname: Cavalcante
authors.affiliation: Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
authors.forename: Michel de Jesus Souza
authors.initials: Mde J
authors.lastname: Machado
authors.affiliation: Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
authors.forename: Aline Santos
authors.initials: AS
authors.lastname: Monte
authors.affiliation: Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
authors.forename: David Freitas
authors.initials: DF
authors.lastname: de Lucena
authors.affiliation: Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil ; Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.affiliation: Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, 60430-160 Fortaleza, CE, Brazil.
authors.forename: André Ferrer
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Neuropharmacology Laboratory, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Rua Coronel Nunes de Melo 1127, 60431-270 Fortaleza, CE, Brazil.
authors.forename: Danielle
authors.initials: D
authors.lastname: Macêdo
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002227:Carbazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D000077261:Carvedilol; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D011412:Propanolamines / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012934:Social Isolation; D014635:Valproic Acid / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000319:Adrenergic beta-Antagonists; D018692:Antimanic Agents; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008315:Malondialdehyde; D014635:Valproic Acid; D005978:Glutathione; D000069478:Lisdexamfetamine Dimesylate