Involvement of the mammalian target of rapamycin signaling in the antidepressant-like effect of group II metabotropic glutamate receptor antagonists

@article{Koike2011InvolvementOT,
  title={Involvement of the mammalian target of rapamycin signaling in the antidepressant-like effect of group II metabotropic glutamate receptor antagonists},
  author={Hiroyuki Koike and Michihiko Iijima and Shigeyuki Chaki},
  journal={Neuropharmacology},
  year={2011},
  volume={61},
  pages={1419-1423}
}
Growing evidence has indicated that the blockade of group II metabotropic glutamate (mGlu2/3) receptor exerts antidepressant-like effects in several animal models of depression. However, the molecular mechanisms underlying the action of mGlu2/3 receptor antagonists are not well understood. Here, we investigated the involvement of mammalian target of rapamycin (mTOR) signaling in the acute and sustained antidepressant-like effects of mGlu2/3 receptor antagonists such as (1R, 2R, 3R, 5R, 6R)-2… Expand
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References

SHOWING 1-10 OF 24 REFERENCES
On the mechanism of the antidepressant-like action of group II mGlu receptor antagonist, MGS0039
TLDR
It is found that repeated administration of MGS0039 attenuated OB-related deficits, confirming antidepressant-like activity of the tested compound, and the mechanism of action of group II mGlu receptor antagonists differs from that of typical antidepressants, such as SSRIs. Expand
AMPA receptor stimulation mediates the antidepressant-like effect of a group II metabotropic glutamate receptor antagonist
TLDR
Findings suggest that stimulation of postsynaptic AMPA receptors plays a role in mediating the pharmacological effects of MGS0039, a selective group II metabotropic glutamate receptor (mGluR) antagonist that exhibits antidepressant-like activities in rodent models. Expand
MGS0039: a potent and selective group II metabotropic glutamate receptor antagonist with antidepressant-like activity
TLDR
The results indicate that MGS0039 is a potent and selective antagonist of group II mGluR, and that group IImGLUR antagonists, like M GS0039, have an antidepressant-like potential in experimental animal models. Expand
Cellular Mechanisms Underlying the Antidepressant Effects of Ketamine: Role of α-Amino-3-Hydroxy-5-Methylisoxazole-4-Propionic Acid Receptors
TLDR
Subanesthetic doses of ketamine treatment caused acute and sustained antidepressant-like effects and at these doses, ketamine did not impair fear memory retention and NMDA antagonists might exert rapid antidepressant- like effects by enhancing AMPA relative to NMDA throughput in critical neuronal circuits. Expand
An mGluR2/3 antagonist, MGS0039, exerts antidepressant and anxiolytic effects in behavioral models in rats
TLDR
Additional evidence is provided that MGS0039 exhibits antidepressant and anxiolytic effects in experimental rodent models, which are predictive of clinical efficacy and suggest that the blockade of mGluR2/3 with M GS0039 may be effective in the treatment of depressive and anxiety disorders. Expand
Involvement of AMPA receptor in both the rapid and sustained antidepressant-like effects of ketamine in animal models of depression
TLDR
The present results suggested that direct AMPA receptor activation may play an important role in both the rapid and sustained antidepressant-like effects of ketamine in animal models of depression, although other mechanisms might be involved in the sustained action. Expand
Synthesis, in vitro pharmacology, structure-activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists.
TLDR
The synthesis, in vitro pharmacological profile, and structure-activity relationships (SARs) of 3-alkoxy-2-amino-6-fluorobicyclo,hexane-2,6-dicarboxylic acid derivatives 11 and 12, and pharmacokinetic profiles of several typical compounds are reported. Expand
The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder
TLDR
Examination of the expression of mTOR and its core downstream signaling targets in the PFC of 12 depressed subjects and 12 psychiatrically healthy controls shows deficits in mTOR-dependent translation initiation in MDD particularly via the p70S6K/eIF4B pathway, and indicates a potential association between marked deficits in synaptic proteins and dysregulation of m TOR signaling inMDD. Expand
mGluR-Dependent Long-Term Depression Is Associated with Increased Phosphorylation of S6 and Synthesis of Elongation Factor 1A but Remains Expressed in S6K-Deficient Mice
TLDR
The findings indicate that mGluR-LTD is associated with PI3K-, mTOR-, and ERK-dependent alterations in the phosphorylation of S6 and S6K. Expand
Glutamate N-methyl-D-aspartate Receptor Antagonists Rapidly Reverse Behavioral and Synaptic Deficits Caused by Chronic Stress Exposure
TLDR
The results indicate that the structural and functional deficits resulting from long-term stress exposure, which could contribute to the pathophysiology of depression, are rapidly reversed by NMDA receptor antagonists in a mammalian target of rapamycin dependent manner. Expand
...
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