PMID- 24901414
OWN - NLM
STAT- MEDLINE
DCOM- 20150526
LR  - 20211203
IS  - 1469-5111 (Electronic)
IS  - 1461-1457 (Linking)
VI  - 17
IP  - 11
DP  - 2014 Nov
TI  - Differential effects of antidepressant drugs on mTOR signalling in rat 
      hippocampal neurons.
PG  - 1831-46
LID - 10.1017/S1461145714000534 [doi]
AB  - Recent studies suggest that ketamine produces antidepressant actions via 
      stimulation of mammalian target of rapamycin (mTOR), leading to increased levels 
      of synaptic proteins in the prefrontal cortex. Thus, mTOR activation may be 
      related to antidepressant action. However, the mTOR signalling underlying 
      antidepressant drug action has not been well investigated. The aim of the present 
      study was to determine whether alterations in mTOR signalling were observed 
      following treatment with antidepressant drugs, using ketamine as a positive 
      control. Using Western blotting, we measured changes in the mTOR-mediated 
      proteins and synaptic proteins in rat hippocampal cultures. Dendritic outgrowth 
      was determined by neurite assay. Our findings demonstrated that escitalopram, 
      paroxetine and tranylcypromine significantly increased levels of phospho-mTOR and 
      its down-stream regulators (phospho-4E-BP-1 and phospho-p70S6K); fluoxetine, 
      sertraline and imipramine had no effect. All drugs tested increased up-stream 
      regulators (phospho-Akt and phospho-ERK) levels. Increased phospho-mTOR induced 
      by escitalopram, paroxetine or tranylcypromine was significantly blocked in the 
      presence of specific PI3K, MEK or mTOR inhibitors, respectively. All drugs tested 
      also increased hippocampal dendritic outgrowth and synaptic proteins levels. The 
      mTOR inhibitor, rapamycin, significantly blocked these effects on escitalopram, 
      paroxetine and tranylcypromine whereas fluoxetine, sertraline and imipramine 
      effects were not affected. The effects of escitalopram, paroxetine and 
      tranylcypromine paralleled those of ketamine. This study presents novel in vitro 
      evidence indicating that some antidepressant drugs promote dendritic outgrowth 
      and increase synaptic protein levels through mTOR signalling; however, other 
      antidepressant drugs seem to act via a different pathway. mTOR signalling may be 
      a promising target for the development of new antidepressant drugs.
FAU - Park, Sung Woo
AU  - Park SW
AD  - Paik Institute for Clinical Research, Inje University,Busan,Republic of Korea.
FAU - Lee, Jung Goo
AU  - Lee JG
AD  - Paik Institute for Clinical Research, Inje University,Busan,Republic of Korea.
FAU - Seo, Mi Kyoung
AU  - Seo MK
AD  - Paik Institute for Clinical Research, Inje University,Busan,Republic of Korea.
FAU - Lee, Chan Hong
AU  - Lee CH
AD  - Paik Institute for Clinical Research, Inje University,Busan,Republic of Korea.
FAU - Cho, Hye Yeon
AU  - Cho HY
AD  - Paik Institute for Clinical Research, Inje University,Busan,Republic of Korea.
FAU - Lee, Bong Ju
AU  - Lee BJ
AD  - Department of Psychiatry, School of Medicine,Haeundae Paik Hospital, Inje 
      University,Busan,Republic of Korea.
FAU - Seol, Wongi
AU  - Seol W
AD  - InAm Neuroscience Research Centre, Wonkwang University, Sanbon Hospital,Gunpo, 
      Kyeonggi-do,Republic of Korea.
FAU - Kim, Young Hoon
AU  - Kim YH
AD  - Paik Institute for Clinical Research, Inje University,Busan,Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140605
PL  - England
TA  - Int J Neuropsychopharmacol
JT  - The international journal of neuropsychopharmacology
JID - 9815893
RN  - 0 (Antidepressive Agents)
RN  - 0 (Carrier Proteins)
RN  - 0 (Eif4ebp1 protein, rat)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Carrier Proteins/metabolism
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Embryo, Mammalian
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Hippocampus/*cytology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Neurites/drug effects
MH  - Neurons/cytology/*drug effects
MH  - Oncogene Protein v-akt/metabolism
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2014/06/06 06:00
MHDA- 2015/05/27 06:00
CRDT- 2014/06/06 06:00
PHST- 2014/06/06 06:00 [entrez]
PHST- 2014/06/06 06:00 [pubmed]
PHST- 2015/05/27 06:00 [medline]
AID - S1461145714000534 [pii]
AID - 10.1017/S1461145714000534 [doi]
PST - ppublish
SO  - Int J Neuropsychopharmacol. 2014 Nov;17(11):1831-46. doi: 
      10.1017/S1461145714000534. Epub 2014 Jun 5.