Involvement of oxidative pathways and BDNF in the antidepressant effect of carvedilol in a depression model induced by chronic unpredictable stress

Rationale Depression is a severe psychiatric disorder with oxidative imbalance and neurotrophic deficits as underlying mechanisms. Objectives Based on the antioxidant effects of carvedilol (CARV), here, we aimed to evaluate CARV’s effects against depression induced by the chronic unpredictable stres...

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Bibliographic Details
Published in:	Psychopharmacology Vol. 239; no. 1; pp. 297 - 311
Main Authors:	de Sousa, Caren Nádia Soares, Medeiros, Ingridy da Silva, Vasconcelos, Germana Silva, de Aquino, Gabriel Angelo, Cysne Filho, Francisco Maurício Sales, de Almeida Cysne, Jamily Cunha, Macêdo, Danielle Silveira, Vasconcelos, Silvânia Maria Mendes
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer Berlin Heidelberg 2022 Springer Springer Nature B.V
Subjects:	Animals Antidepressants Antidepressive Agents - pharmacology Antioxidants Biomedical and Life Sciences Biomedicine Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - metabolism Carvedilol - pharmacology Depression - drug therapy Depression, Mental Disease Models, Animal Drug therapy Female Glutathione Grooming Health aspects Hippocampus Hippocampus - metabolism Latency Locomotion Malondialdehyde Mental depression Mice Motivation Neurosciences Original Investigation Oxidative Stress Pharmacology/Toxicology Prefrontal cortex Psychiatry Short term memory Social interaction Stress, Psychological - drug therapy Brazil Chronic unpredictable stress Oxidative stress Depression Brain-derived neurotrophic factor Carvedilol
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Summary:	Rationale Depression is a severe psychiatric disorder with oxidative imbalance and neurotrophic deficits as underlying mechanisms. Objectives Based on the antioxidant effects of carvedilol (CARV), here, we aimed to evaluate CARV’s effects against depression induced by the chronic unpredictable stress (CUS) model. Methods Female Swiss mice were submitted to the CUS protocol for 21 days. Between days 15 and 22, the animals received CARV (5 or 10 mg/kg) or desvenlafaxine (DVS 10 mg/kg) orally. On the 22nd day, mice were subjected to behavioral tests to evaluate locomotion, depressive-like behavior (tail suspension test), motivation/self-care with the splash test (ST), social interaction, and working memory Y-maze test. The prefrontal cortex (PFC) and hippocampus were dissected to evaluate alterations of oxidative and brain-derived neurotrophic factor (BDNF). Results The CUS model reduced locomotion and increased grooming latency, while it reduced the number of groomings in the ST. Both doses of CARV and DVS reverted these alterations. In addition, DVS and CARV reversed CUS model–induced working memory and social interaction deficits. The CUS model decreased hippocampal reduced glutathione (GSH), while DVS and CARV increased GSH in the PFC (CARV5) and hippocampus (CARV5 and 10). The CUS model increased nitrite and malondialdehyde (MDA) concentrations in both areas. All treatments reversed nitrite alterations, while CARV10 changed MDA levels in PFC and all treatments in the hippocampus. The CUS model reduced BDNF levels. CARV10 increased BDNF in the PFC, while both doses of CARV increased hippocampal levels of this neurotrophin. Conclusions CARV presents antidepressant-like effects comparable to those observed with DVS. In addition, it has an antioxidant effect and is capable of increasing BDNF brain concentrations. Further studies are needed to elucidate the mechanisms involved in the antidepressant effect of CARV.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0033-3158 1432-2072
DOI:	10.1007/s00213-021-05994-6