Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner

0459832 - FGÚ 2017 RIV US eng J - Journal Article
Holubová, Kristína - Kletečková, Lenka - Škurlová, Martina - Říčný, J. - Stuchlík, Aleš - Valeš, Karel
Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner.
Psychopharmacology. Roč. 233, č. 11 (2016), s. 2077-2097. ISSN 0033-3158. E-ISSN 1432-2072
R&D Projects: GA MZd(CZ) NT13403
Institutional support: RVO:67985823
Keywords : ketamine * rapamycin * antidepressants * anxiety * cognitive deficit * bulbectomy * mTOR * BDNF
Subject RIV: FH - Neurology
Impact factor: 3.308, year: 2016

Bulbectomized (OBX) rats and sham controls were assigned to four subgroups according to the treatment they. The animals were subjected to open field (OF), elevated plus maze (EPM), passive avoidance (PA), Morris water maze (MWM), and Carousel maze (CM) tests. Blood samples were collected before and after drug administration for analysis of phosphorylated mTOR level. After behavioral testing, brains were removed for evaluation of brain-derived neurotrophic factor (BDNF) in prefrontal cortex (PFC) and hippocampus.Ketamine normalized hyperactivity of OBX animals in EPM and increased the time spent in open arms. Rapamycin pretreatment resulted in elimination of ketamine effect in EPM test. In CM test, ketamine + rapamycin administration led to cognitive impairment not observed in saline-, ketamine-, or saline + rapamycin-treated OBX rats. Prefrontal BDNF content was significantly decreased, and level of mTOR was significantly elevated in OBX groups. OBX animals significantly differed from sham controls in most of the tests used. Treatment had more profound effect on OBX phenotype than controls. Pretreatment with rapamycin eliminated the anxiolytic and antidepressant effects of ketamine in task-dependent manner.
Permanent Link: http://hdl.handle.net/11104/0259996