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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Ketamine and aminoguanidine differentially affect Bdnf and Mtor gene expression in the prefrontal cortex of adult male rats

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Author(s):
Pereira, Vitor Silva [1, 2] ; Elfving, Betina [1] ; Joca, Samia R. L. [1, 2] ; Wegener, Gregers [1, 3, 4]
Total Authors: 4
Affiliation:
[1] Aarhus Univ, Dept Clin Med, Translat Neuropsychiat Unit, Skovagervej 2, DK-8240 Risskov - Denmark
[2] Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Campus USP Ribeirao Preto, BR-14040904 Ribeirao Preto, SP - Brazil
[3] Aarhus Univ, AUGUST Ctr, Dept Clin Med, Risskov - Denmark
[4] North West Univ, Sch Pharm, Ctr Pharmaceut Excellence, ZA-2531 Potchefstroom - South Africa
Total Affiliations: 4
Document type: Journal article
Source: European Journal of Pharmacology; v. 815, p. 304-311, NOV 15 2017.
Web of Science Citations: 4
Abstract

The rapid and sustained antidepressant properties of ketamine provide evidence of the importance of the glutamatergic system in the neurobiology of depression. The antidepressant-like effects of ketamine are dependent on brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in limbic brain areas. The nitrergic system is closely related to the glutamatergic system and generates antidepressant-like effects when blocked. The aim of this study was to investigate whether the behavioural effects induced by the inhibition of nitric oxide (NO) synthesis by aminoguanidine or N-methyl-D-aspartate (NMDA) receptor blockade by ketamine would affect the gene expression of Bdnf and Mtor in the ventromedial prefrontal cortex in rats. The effects of ketamine or aminoguanidine were investigated in Sprague-Dawley (SD) rats, the Flinders Sensitive Line (FSL), a genetic rat model of depression, and their controls, the Flinders Resistant Line (FRL) rats. In the studies, the three protocols evaluated to which the animals/rats were exposed were: (1) pre-test and test sessions of forced swim test (FST), (2) pre-test session of FST alone, or (3) not exposed to the FST. Ketamine and aminoguanidine both induce antidepressant-like effects in SD and FSL rats. Quantitative real-time polymerase chain reaction analyses in SD rats demonstrated that none of the treatments can change the Bdnf or Mtor gene expression, but in FSL rats the treatment with ketamine increased only Bdnf gene expression. The data obtained strengthens the role of NMDA antagonists and NO inhibitors as potential antidepressant drugs, albeit with different effects on Bdnf gene expression. (AU)

FAPESP's process: 13/00916-5 - Involvement of BDNF-TrkB-mTOR pathway in the antidepressant-like effect induced by nos inhibitors
Grantee:Vitor Silva Pereira
Support Opportunities: Scholarships abroad - Research Internship - Doctorate