1. Mechanism of synergistic action on behavior, oxidative stress and inflammation following co-treatment with ketamine and different antidepressant classes
- Author
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Zuleide M. Ignácio, Airam B. de Moura, André F. Carvalho, Amanda L. Maciel, Gislaine Z. Réus, Beatriz I. Matias, João Quevedo, Helena M. Abelaira, Lucineia Gainski Danielski, Danyela Matos, and Fabricia Petronilho more...
- Subjects
Male ,medicine.drug_class ,Lamotrigine ,Pharmacology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Ketamine ,Rats, Wistar ,Swimming ,Inflammation ,Fluoxetine ,Behavior, Animal ,Drug Synergism ,General Medicine ,medicine.disease ,Receptor antagonist ,Antidepressive Agents ,Rats ,030227 psychiatry ,Oxidative Stress ,Antidepressant ,Major depressive disorder ,Quetiapine ,NMDA receptor ,Drug Therapy, Combination ,Psychology ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Major depressive disorder (MDD) affects many people in the world. However, around 40% of patients do not respond to any pharmacological drugs. An alternative is to use a combination of different pharmacological groups or the combination of a classical antidepressant with a substance that can potentiate its effect. Thus, this study aimed to investigate the synergistic interactions between different antidepressants, including fluoxetine, quetiapine and lamotrigine in combination with ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist.Wistar rats were acutely treated with fluoxetine (1.25mg/kg), quetiapine (5mg/kg), and lamotrigine (5.0mg/kg) alone or in combination with ketamine (5.0mg/kg), and then subjected to behavioral tests. In addition, oxidative damage and antioxidant capacity were assessed in the rat brain, and pro-inflammatory cytokines levels were evaluated in the serum.It was observed a synergistic effect of ketamine in combination with fluoxetine on the immobility time in the forced swimming test, indicating an antidepressant effect. Other antidepressant did not show effects when administrated alone or joint to ketamine. The combination of ketamine with other antidepressants, particularly quetiapine, in some brain regions induced an increase in damage to lipids and proteins. However, the combination of ketamine with fluoxetine increased the antioxidant activity of superoxide dismutase, and decreased oxidative damage, thus suggesting a neuroprotective effect of the combination of these drugs. The combination of ketamine with fluoxetine or lamotrigine reduced pro-inflammatory cytokines levels.In conclusion, ketamine induced antioxidant or pro-antioxidant effects dependent of antidepressant classes or brain area. more...
- Published
- 2017
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