Advantages of the Alpha-lipoic Acid Association with Chlorpromazine in a Model of Schizophrenia Induced by Ketamine in Rats: Behavioral and Oxidative Stress evidences

Advantages of the Alpha-lipoic Acid Association with Chlorpromazine in a Model of Schizophrenia Induced by Ketamine in Rats: Behavioral and Oxidative Stress evidences

•KET induced hyperlocomotion, impaired working memory and decreased prepulse inhibition associated to oxidative stress.•Pre-treatment with CP, alone or associated to ALA, reverse effects of ketamine-induced schizophrenia.•Alpha-lipoic acid potentiates the antioxidant effect of chlorpromazine in the...

Full description

Saved in:
Bibliographic Details
Published in:Neuroscience Vol. 373; pp. 72 - 81
Main Authors: Sampaio, Luis Rafael Leite, Cysne Filho, Francisco Maurício Sales, de Almeida, Jamily Cunha, Diniz, Danilo dos Santos, Patrocínio, Cláudio Felipe Vasconcelos, de Sousa, Caren Nádia Soares, Patrocínio, Manoel Cláudio Azevedo, Macêdo, Danielle, Vasconcelos, Silvânia Maria Mendes
Format: Journal Article
Language:English
Published: United States Elsevier Ltd 01-03-2018
Subjects:
alpha-lipoic acid
chlorpromazine
Hippocampus
ketamine
oxidative stress
schizophrenia
NO
alpha-lipoic acid
MDA
schizophrenia
HTAB
CP
MPO
NOS
chlorpromazine
ketamine
ALA
NMDAR
KET
RM
PCP
GSH
Hippocampus
oxidative stress
HClO
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•KET induced hyperlocomotion, impaired working memory and decreased prepulse inhibition associated to oxidative stress.•Pre-treatment with CP, alone or associated to ALA, reverse effects of ketamine-induced schizophrenia.•Alpha-lipoic acid potentiates the antioxidant effect of chlorpromazine in the hippocampus of rats.•Alpha-lipoic and chlorpromazine as a perspective of augmentation therapy in treatment of schizophrenia. Schizophrenia is a chronic mental disorder reported to compromise about 1% of the world's population. Although its pathophysiological process is not completely elucidated, evidence showing the presence of an oxidative imbalance has been increasingly highlighted in the literature. Thus, the use of antioxidant substances may be of importance for schizophrenia treatment. The objective of this study was to evaluate the behavioral and oxidative alterations by the combination of chlorpromazine (CP) and alpha-lipoic acid (ALA), a potent antioxidant, in the ketamine (KET) model of schizophrenia in rats. Male Wistar rats (200–300 g) were treated for 10 days with saline, CP or ALA alone or in combination with CP previous to KET and the behavioral (open field, Y-maze and PPI tests) and oxidative tests were performed on the last day of treatment. The results showed that KET induced hyperlocomotion, impaired working memory and decreased PPI. CP alone or in combination with ALA prevented KET-induced behavioral effects. In addition, the administration of KET decreased GSH and increased nitrite, lipid peroxidation and myeloperoxidase activity. CP alone or combined with ALA prevented the oxidative alterations induced by KET. In conclusion, the treatment with KET in rats induced behavioral impairments accompanied by hippocampal oxidative alterations, possibly related to NMDA receptors hypofunction. Besides that, CP alone or combined with ALA prevented these effects, showing a beneficial activity as antipsychotic agents.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2018.01.008