Differential regulation of GluA1 expression by ketamine and memantine

Zhang, Ke; Yamaki, Vítor Nagai; Wei, Zhisheng; Zheng, Yu; Cai, Xiang

doi:10.1016/j.bbr.2016.09.002

Cited by 43 publications

(36 citation statements)

References 38 publications

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“…This may contribute to increased glutamatergic transmission by insertion of AMPARs at synapses in the hippocampus and medial prefrontal cortex. 3,11,38 In the NAc, we found that LTP in saline-treated mice is blocked by an mTOR inhibitor, rapamycin, suggesting a role for mTOR in this form of synaptic plasticity. In line with this possibility, an LTP induction protocol was shown to increase mTOR phosphorylation in the medial prefrontal cortex.…”

Section: Discussionmentioning

confidence: 87%

“…Several reports have demonstrated that ketamine, and also (2R,6R)-HNK, applied in the perfusion solution enhance AMPARmediated synaptic transmission in the hippocampus. 6,20,38,[54][55][56][57][58] Other reports demonstrate a lack of effect of this treatment in the Ketamine alters mesolimbic synaptic plasticity N Yao et al same brain region 59 and suggest that the acute effect of ketamine is dependent on the concentration of this compound used and the location of the recording within the hippocampus (somatic vs dendritic recordings). 58 The ketamine-induced increase in hippocampal synaptic transmission is mimicked or blocked by NMDAR antagonists 55,57,58 and requires presynaptic NMDARs.…”

Section: Discussionmentioning

confidence: 99%

“…54 Furthermore, the increased glutamatergic transmission is not long-lasting, because the EPSP returns to baseline 2-3 h after ketamine perfusion. 54 Zhang et al 26,38,54 further demonstrated that ketamine applied in the perfusion solution or administered intraperitoneally increases the phosphorylation of Ser 845 -GluA1 and the expression of total GluA1 in the hippocampus. Our observations in the NAc were made using an experimental paradigm different from the studies in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

“…[44][45][46] Interestingly, chronic stress and administration of ketamine were found to modulate the phosphorylation of GluA1 in the hippocampus 5,38 and amygdala. 47 We therefore examined the possibility that a potential mechanism for LTP induction by HFS and inhibition by ketamine involved an altered phosphorylation of GluA1 in the NAc.…”

Section: 11mentioning

confidence: 99%

“…Ketamine activates mammalian target of rapamycin (mTOR) signaling. [35][36][37][38] We therefore examined the possibility that inhibition of mTOR with rapamycin could prevent ketamineinduced impairment of LTP. We found that in the presence of rapamycin in the perfusion solution, LTP remained impaired in the NAc of ketamine-treated mice (10 mg kg − 1 1 day; without rapamycin: 109.9 ± 6.7; n = 15; with rapamycin: 200 nM: 109.5 ± 9.1; n = 9; with rapamycin: 1 μM: 95.1 ± 9.4; n = 5; P40.05, one-way analysis of variance, Dunnett's multiple comparison test; Figure 4a).…”

Section: 11mentioning

confidence: 99%

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Ketamine and its metabolite (2R,6R)-hydroxynorketamine induce lasting alterations in glutamatergic synaptic plasticity in the mesolimbic circuit

et al. 2017

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Low doses of ketamine trigger rapid and lasting antidepressant effects after one injection in treatment-resistant patients with major depressive disorder. Modulation of AMPA receptors (AMPARs) in the hippocampus and prefrontal cortex is suggested to mediate the antidepressant action of ketamine and of one of its metabolites (2R,6R)-hydroxynorketamine ((2R,6R)-HNK). We have examined whether ketamine and (2R,6R)-HNK affect glutamatergic transmission and plasticity in the mesolimbic system, brain regions known to have key roles in reward-motivated behaviors, mood and hedonic drive. We found that one day after the injection of a low dose of ketamine, long-term potentiation (LTP) in the nucleus accumbens (NAc) was impaired. Loss of LTP was maintained for 7 days and was not associated with an altered basal synaptic transmission mediated by AMPARs and N-methyl-D-aspartate receptors (NMDARs). Inhibition of mammalian target of rapamycin signaling with rapamycin did not prevent the ketamine-induced loss of LTP but inhibited LTP in saline-treated mice. However, ketamine blunted the increase in the phosphorylation of the GluA1 subunit of AMPARs at a calcium/calmodulin-dependent protein kinase II/protein kinase C site induced by an LTP induction protocol. Moreover, ketamine caused a persistent increased phosphorylation of GluA1 at a protein kinase A site. (2R,6R)-HNK also impaired LTP in the NAc. In dopaminergic neurons of the ventral tegmental area from ketamine-or (2R,6R)-HNK-treated mice, AMPAR-mediated responses were depressed, while those mediated by NMDARs were unaltered, which resulted in a reduced AMPA/NMDA ratio, a measure of long-term synaptic depression. These results demonstrate that a single injection of ketamine or (2R,6R)-HNK induces enduring alterations in the function of AMPARs and synaptic plasticity in brain regions involved in reward-related behaviors.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: 11mentioning

confidence: 99%

Section: 11mentioning

confidence: 99%

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Ketamine and its metabolite (2R,6R)-hydroxynorketamine induce lasting alterations in glutamatergic synaptic plasticity in the mesolimbic circuit

et al. 2017

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The Challenge of Antidepressant Therapeutics in Alzheimer’s Disease

Lozupone

Montagna

D’Urso

et al. 2020

Advances in Experimental Medicine and Biology

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The role of mGluR5 on the therapeutic effects of ketamine in Wistar rats

Gokalp,

Unal

2024

Psychopharmacology

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Rationale Ketamine produces dissociative, psychomimetic, anxiolytic, antidepressant, and anesthetic effects in a dose dependent manner. It has a complex mechanism of action that involve alterations in other glutamate receptors. The metabotropic glutamate receptor 5 (mGluR5) has been investigated in relation to the psychotic and anesthetic properties of ketamine, while its role in mediating the therapeutic effects of ketamine remains unknown. Objectives We investigated the role of mGluR5 on the antidepressant, anxiolytic and fear memory-related effects of ketamine in adult male Wistar rats. Methods Two sets of experiments were conducted. We first utilized the positive allosteric modulator CDPPB to investigate how acute mGluR5 activation regulates the therapeutic effects of ketamine (10 mg/kg). We then tested the synergistic antidepressant effect of mGluR5 antagonism and ketamine by combining MTEP with a sub-effective dose of ketamine (1 mg/kg). Behavioral despair, locomotor activity, anxiety-like behavior, and fear memory were respectively assessed in the forced swim test (FST), open field test (OFT), elevated plus maze (EPM), and auditory fear conditioning. Results Enhancing mGluR5 activity via CDPPB occluded the antidepressant effect of ketamine without changing locomotor activity. Furthermore, concomitant administration of MTEP and ketamine exhibited a robust synergistic antidepressant effect. The MTEP + ketamine treatment, however, blocked the anxiolytic effect observed by sole administration of MTEP or the low dose ketamine. Conclusions These findings suggest that suppressed mGluR5 activity is required for the antidepressant effects of ketamine. Consequently, the antagonism of mGluR5 enhances the antidepressant effectiveness of low dose ketamine, but eliminates its anxiolytic effects.

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Differential regulation of GluA1 expression by ketamine and memantine

Cited by 43 publications

References 38 publications

Ketamine and its metabolite (2R,6R)-hydroxynorketamine induce lasting alterations in glutamatergic synaptic plasticity in the mesolimbic circuit

Ketamine and its metabolite (2R,6R)-hydroxynorketamine induce lasting alterations in glutamatergic synaptic plasticity in the mesolimbic circuit

The Challenge of Antidepressant Therapeutics in Alzheimer’s Disease

The role of mGluR5 on the therapeutic effects of ketamine in Wistar rats

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