Ketamine Treatment Partly Reverses Alterations in Brain Derived- Neurotrophic Factor, Oxidative Stress and Energy Metabolism Parameters Induced by an Animal Model of Depression

Author(s): Gislaine Z. Réus, Marcos Paulo Nacif, v M. Abelaira, Débora B. Tomaz, Maria Augusta B. dos Santos, Anelise S. Carlessi, Beatriz I. Matias, Jaine R. da Luz, Amanda V. Steckert, Gabriela C. Jeremias, Giselli Scaini, Meline O.S. Morais, Emilio L. Streck, João Quevedo

Journal Name: Current Neurovascular Research

Volume 12 , Issue 1 , 2015

Become EABM
Become Reviewer
Call for Editor


Studies have suggested that ketamine, a nonselective NMDA receptor antagonist, could be a new drug in the treatment of major depression, but the way ketamine presents such effects remains to be elucidated. Therefore, the objective of this paper was to evaluate the effects of ketamine treatment on parameters related to depression in the brain of adult rats subjected to an animal model of depression. The animals were divided into: non-deprived + saline; non-deprived + ketamine; deprived + saline; deprived + ketamine. Treatments involving ketamine (15 mg/kg) were administered once a day during 14 days in the animal’s adult phase. After treatment, the brain derived-neurotrophic factor (BDNF) levels, oxidative stress and energy metabolism activity were evaluated in brain structures of rats involved in the circuit of depression. In the amygdala, hippocampus and nucleus accumbens (NAc), a reduction in BDNF levels was observed in deprived rats, but the animals treated with ketamine reversed the effects of this animal model only in the amygdala and NAc. In addition to this, the complex I activity, in deprived rats, was diminished in the prefrontal cortex (PFC) and amygdala; in the PFC and hippocampus, the complex II-III was diminished in deprived rats; still the administration of ketamine increased the complex IV activity in the PFC and amygdala of rats submitted to the maternal deprivation. In deprived rats, the creatine kinase activity was reduced in the PFC and amygdala, however the administration of ketamine reversed this decrease in the amygdala. The malondialdehyde (MDA) equivalents were increased in non-deprived rats treated with ketamine in the PFC and NAc. Carbonyl levels in the PFC were diminished in control rats that received saline. Though ketamine treatment reversed this effect in deprived rats in the PFC and hippocampus. Still, in NAc, the carbonyl levels were diminished in deprived rats. The superoxide dismutase (SOD) activity was increased in control rats that received ketamine in the PFC and NAc, and were diminished in deprived rats that received saline or ketamine in the PFC and hippocampus. These findings may help to explain that dysfunctions involving BDNF, oxidative stress and energy metabolism within specific brain areas, may be linked with the pathophysiology of depression, and antidepressant effects of ketamine can be positive, at least partially due to the control of these pathways.

Keywords: Ketamine, NMDA receptor, BDNF, energy metabolism, oxidative stress, depression.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2015
Published on: 10 February, 2015
Page: [73 - 84]
Pages: 12
DOI: 10.2174/1567202612666150122122924
Price: $65

Article Metrics

PDF: 55