PMID- 24631968
OWN - NLM
STAT- MEDLINE
DCOM- 20150109
LR  - 20211203
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 82
DP  - 2014 Jul
TI  - Activation of the mTOR signaling pathway in the antidepressant-like activity of 
      the mGlu5 antagonist MTEP and the mGlu7 agonist AMN082 in the FST in rats.
PG  - 59-68
LID - S0028-3908(14)00085-9 [pii]
LID - 10.1016/j.neuropharm.2014.03.001 [doi]
AB  - Clinical studies have demonstrated rapid and long-lasting antidepressant effects 
      of ketamine in depressive patients. It has been proposed that these effects are 
      related to changes in synaptogenesis in the mechanism involving mammalian target 
      of rapamycin (mTOR) activation. Similar mechanisms have been proposed for a group 
      II metabotropic glutamate (mGlu) receptor antagonist, LY341495. We aimed to 
      investigate whether other mGlu receptor ligands that produce antidepressant-like 
      effects, namely, the mGlu5 antagonist MTEP and the mGlu7 agonist AMN082, induce 
      the activation of mTOR signaling in the prefrontal cortex (PFC) in rats. AMN082 
      administered 60 min before the test increased the levels of pmTOR and pp70S6K, 
      and the mTORC1 antagonist rapamycin reversed AMN082-induced changes in the forced 
      swim test (FST) in rats. Furthermore, AMN082 administered 23 h before the 
      decapitation of the rats increased the levels of synapsin I and GluR1, although 
      it did not produce any effect in the FST at the same time point. However, MTEP 
      induced a rapid but unsustained antidepressant-like effect, which was not related 
      to the activation of the mTOR cascade. Finally, the antidepressant-like effects 
      of MTEP or AMN082 were not antagonized by NBQX. In summary, the 
      antidepressant-like activity of MTEP did not depend on the activation of mTOR 
      signaling. However, we observed a unique feature of the mechanism of AMN082. The 
      drug stimulated the mTOR signaling pathway and synaptic protein levels (like 
      ketamine), while it did not induce a sustained antidepressant effect and its 
      action was not directly dependent on AMPA receptor activation (as in classic 
      antidepressants (ADs)).
CI  - Copyright (c) 2014. Published by Elsevier Ltd.
FAU - Palucha-Poniewiera, Agnieszka
AU  - Palucha-Poniewiera A
AD  - Institute of Pharmacology Polish Academy of Sciences, Department of Neurobiology, 
      Smetna 12, 31-343 Krakow, Poland. Electronic address: nfpaluch@cyf-kr.edu.pl.
FAU - Szewczyk, Bernadeta
AU  - Szewczyk B
AD  - Institute of Pharmacology Polish Academy of Sciences, Department of Neurobiology, 
      Smetna 12, 31-343 Krakow, Poland.
FAU - Pilc, Andrzej
AU  - Pilc A
AD  - Institute of Pharmacology Polish Academy of Sciences, Department of Neurobiology, 
      Smetna 12, 31-343 Krakow, Poland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140312
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Grm5 protein, rat)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride)
RN  - 0 (Pyridines)
RN  - 0 (Quinoxalines)
RN  - 0 (Receptor, Metabotropic Glutamate 5)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - 0 (Synapsins)
RN  - 0 (Thiazoles)
RN  - 0 (metabotropic glutamate receptor 7)
RN  - 118876-58-7 (2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/pharmacology
MH  - Benzhydryl Compounds/*pharmacology
MH  - Depression/*drug therapy/physiopathology
MH  - Excitatory Amino Acid Agonists/*pharmacology
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes/antagonists & inhibitors/metabolism
MH  - Neuropsychological Tests
MH  - Prefrontal Cortex/drug effects/physiology
MH  - Pyridines/*pharmacology
MH  - Quinoxalines/pharmacology
MH  - Rats, Sprague-Dawley
MH  - Receptor, Metabotropic Glutamate 5/antagonists & inhibitors/metabolism
MH  - Receptors, AMPA/metabolism
MH  - Receptors, Metabotropic Glutamate/agonists/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - Swimming
MH  - Synapsins/metabolism
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Thiazoles/*pharmacology
OTO - NOTNLM
OT  - AMN082
OT  - Antidepressant
OT  - MTEP
OT  - mGlu receptors
OT  - mTOR
EDAT- 2014/03/19 06:00
MHDA- 2015/01/13 06:00
CRDT- 2014/03/18 06:00
PHST- 2013/08/14 00:00 [received]
PHST- 2014/02/27 00:00 [revised]
PHST- 2014/03/01 00:00 [accepted]
PHST- 2014/03/18 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
AID - S0028-3908(14)00085-9 [pii]
AID - 10.1016/j.neuropharm.2014.03.001 [doi]
PST - ppublish
SO  - Neuropharmacology. 2014 Jul;82:59-68. doi: 10.1016/j.neuropharm.2014.03.001. Epub 
      2014 Mar 12.