-
Something wrong with this record ?
Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner
K. Holubova, L. Kleteckova, M. Skurlova, J. Ricny, A. Stuchlik, K. Vales,
Language English Country Germany
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NT13403
MZ0
CEP Register
Digital library NLK
Full text - Article
Source
NLK
ProQuest Central
from 1997-02-01 to 1 year ago
Medline Complete (EBSCOhost)
from 1996-10-01 to 1 year ago
Nursing & Allied Health Database (ProQuest)
from 1997-02-01 to 1 year ago
Health & Medicine (ProQuest)
from 1997-02-01 to 1 year ago
Psychology Database (ProQuest)
from 1997-02-01 to 1 year ago
- MeSH
- Antidepressive Agents pharmacology MeSH
- Maze Learning drug effects MeSH
- Olfactory Bulb physiology MeSH
- Hippocampus drug effects metabolism MeSH
- Ketamine antagonists & inhibitors pharmacology MeSH
- Rats MeSH
- Brain-Derived Neurotrophic Factor metabolism MeSH
- Rats, Wistar MeSH
- Prefrontal Cortex drug effects metabolism MeSH
- Sirolimus pharmacology MeSH
- TOR Serine-Threonine Kinases drug effects metabolism MeSH
- Avoidance Learning drug effects MeSH
- Anxiety psychology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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 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. 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.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc17014001
- 003
- CZ-PrNML
- 005
- 20181026092655.0
- 007
- ta
- 008
- 170413s2016 gw f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1007/s00213-016-4256-3 $2 doi
- 035 __
- $a (PubMed)27004790
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a gw
- 100 1_
- $a Holubová, Kristína $u The Institute of Physiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 14220, Prague, Czech Republic. National Institute of Mental Health, Topolova 748, 250 67 Klecany, Prague East, Czech Republic. $7 xx0278720
- 245 10
- $a Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner / $c K. Holubova, L. Kleteckova, M. Skurlova, J. Ricny, A. Stuchlik, K. Vales,
- 520 9_
- $a 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 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. 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.
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a antidepresiva $x farmakologie $7 D000928
- 650 _2
- $a úzkost $x psychologie $7 D001007
- 650 _2
- $a učení vyhýbat se $x účinky léků $7 D001362
- 650 _2
- $a mozkový neurotrofický faktor $x metabolismus $7 D019208
- 650 _2
- $a hipokampus $x účinky léků $x metabolismus $7 D006624
- 650 _2
- $a ketamin $x antagonisté a inhibitory $x farmakologie $7 D007649
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a bludiště - učení $x účinky léků $7 D018782
- 650 _2
- $a bulbus olfactorius $x fyziologie $7 D009830
- 650 _2
- $a prefrontální mozková kůra $x účinky léků $x metabolismus $7 D017397
- 650 _2
- $a krysa rodu Rattus $7 D051381
- 650 _2
- $a potkani Wistar $7 D017208
- 650 _2
- $a sirolimus $x farmakologie $7 D020123
- 650 _2
- $a TOR serin-threoninkinasy $x účinky léků $x metabolismus $7 D058570
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Kleteckova, Lenka $u The Institute of Physiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 14220, Prague, Czech Republic. National Institute of Mental Health, Topolova 748, 250 67 Klecany, Prague East, Czech Republic.
- 700 1_
- $a Škurlová, Martina $u The Institute of Physiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 14220, Prague, Czech Republic. National Institute of Mental Health, Topolova 748, 250 67 Klecany, Prague East, Czech Republic. $7 xx0226211
- 700 1_
- $a Říčný, Jan $u National Institute of Mental Health, Topolova 748, 250 67 Klecany, Prague East, Czech Republic. $7 xx0153151
- 700 1_
- $a Stuchlík, Aleš, $u The Institute of Physiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 14220, Prague, Czech Republic. $d 1974- $7 xx0014340
- 700 1_
- $a Valeš, Karel $u The Institute of Physiology, Academy of Sciences of the Czech Republic, v.v.i., Videnska 1083, 14220, Prague, Czech Republic. vales@biomed.cas.cz. National Institute of Mental Health, Topolova 748, 250 67 Klecany, Prague East, Czech Republic. vales@biomed.cas.cz. $7 xx0070865
- 773 0_
- $w MED00003990 $t Psychopharmacology $x 1432-2072 $g Roč. 233, č. 11 (2016), s. 2077-2097
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/27004790 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20170413 $b ABA008
- 991 __
- $a 20181026093205 $b ABA008
- 999 __
- $a ok $b bmc $g 1200466 $s 974779
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2016 $b 233 $c 11 $d 2077-2097 $e 20160323 $i 1432-2072 $m Psychopharmacology $n Psychopharmacology $x MED00003990
- GRA __
- $a NT13403 $p MZ0
- LZP __
- $a Pubmed-20170413
