Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F16%3A43915014" target="_blank" >RIV/00023752:_____/16:43915014 - isvavai.cz</a>
Alternative codes found
RIV/67985823:_____/16:00459832
Result on the web
<a href="http://link.springer.com/article/10.1007%2Fs00213-016-4256-3" target="_blank" >http://link.springer.com/article/10.1007%2Fs00213-016-4256-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00213-016-4256-3" target="_blank" >10.1007/s00213-016-4256-3</a>
Alternative languages
Result language
angličtina
Original language name
Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner
Original language description
Objective The aim of our study was to test whether ketamine produces an antidepressant effect in animal model of olfactory bulbectomy and assess the role of mammalian target of rapamycin (mTOR) pathway in ketamine's antidepressant effect. Methods Bulbectomized (OBX) rats and sham controls were assigned to four subgroups according to the treatment they received (ketamine, saline, ketamine + rapamycin, and saline + rapamycin). 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. Results Ketamine normalized hyperactivity of OBX animals in EPMand 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.Conclusions 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. The results indicate that ketamine + rapamycin application resulted in impaired stress responses manifested by cognitive deficits in active place avoidance (CM) test. Intensity of stressor (mild vs. severe) used in the behavioral tests had opposite effect on controls and on OBX animals.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FH - Neurology, neuro-surgery, nuero-sciences
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Psychopharmacology
ISSN
0033-3158
e-ISSN
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Volume of the periodical
233
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
21
Pages from-to
2077-2097
UT code for WoS article
000376102100007
EID of the result in the Scopus database
2-s2.0-84961825609&