scholarly journals Blocking N-Methyl-D-aspartic Acid (NMDA) Receptor Inhibits Heat-Sensitization Response of Moxibustion in Stroke Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Zhimai Lyu ◽  
Dandan Huang ◽  
Dingyi Xie ◽  
Yanjun Chen ◽  
Chunmei Wu ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Aspartic Acid ◽  
Negative Impact ◽  
Long Term Potentiation ◽  
Nmda Receptor Antagonist ◽  
Cerebral Infarct ◽  
Significant Drop ◽  
Vehicle Injection ◽  
Heat Sensitization

Our previous studies demonstrated that effects of moxibustion heavily relied on heat-sensitization response, a specific sensation induced by moxibustion in the ill body. On the sensation, long-term potentiation (LTP) of prelimbic cortex was attributed to heat-sensitization responses. The N-methyl-D-aspartic acid (NMDA) receptor plays a key role in LTP induction; however, little is known about the role of NMDA receptor in heat-sensitization response. The present study investigated the role of NMDA receptor in heat-sensitization response, specifically, NMDA receptor was inhibited by competitive glutamatergic antagonist, (±)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), observing the frequency of heat-sensitization response in moxibustion treatment and evaluating the conducive outcomes to cerebral infarct rats for rehabilitation. Heat-sensitization response in cerebral infarct rats was regularly measured for all the samples when exposed to moxibustion. Intraperitoneal injection of CPP was conducted, and soon afterwards, a significant drop of heat-sensitization response in all the samples was measured. Moreover, moxibustion efficiency on rehabilitation was unfavourably affected in cerebral infarct rats when compared to vehicle injection control. This indicated that NMDA receptor antagonist made a negative impact on induction of heat-sensitization response and consequently affected cerebral infarct rats to rehabilitate under moxibustion treatment. It also suggested that activating NMDA receptor played a positive part in ischemic stroke rehabilitation, and regulating its activity could be a feasible way to increase heat-sensitization response, improving the effect of moxibustion.

Metabotropic glutamate receptor dependent EPSP and EPSP-spike potentiation in area CA1 of the submerged rat hippocampal slice

1996 ◽  
Vol 76 (5) ◽  
pp. 3126-3135 ◽  
Author(s):  
N. A. Breakwell ◽  
M. J. Rowan ◽  
R. Anwyl
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Cell Body ◽  
Metabotropic Glutamate Receptor ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Area Ca1 ◽  
Gabaa Receptor Antagonist

1. We reexamined the important areas of conflict in (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]-induced potentiation of the field excitatory postsynaptic potential (EPSP) and, for the first time, investigated the role of mGluRs in EPSP-spike (E-S) coupling. 2. (1S,3R)-ACPD (10 microM) bath applied for 20 min consistently induced a long-lasting potentiation of the dendritic EPSP in area CA1 of submerged rat hippocampal slices, which was considerably faster in onset than described previously. 3. This effect was not associated with any change in presynaptic fiber volley but was dependent on both an intact CA3 connection, because removal of area CA3 blocked (1S,3R)-ACPD-induced potentiation, and also on functional N-methyl-D-aspartate (NMDA) receptors, because (1S,3R)-ACPD-induced potentiation was blocked by inclusion of the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (AP5; 50 microM). 4. (1S,3R)-ACPD induced a long-lasting potentiation of the population spike (PS) amplitude that was consistently larger than that of the EPSP measured in the cell body area. This EPSP-PS (E-S) potentiation was blocked by inclusion of the gamma-aminobuturic acid-A (GABAA) receptor antagonist, picrotoxin (50 microM). 5. E-S potentiation induced by high-frequency stimulation (HFS), which was of the same magnitude as that induced by (1S,3R)-ACPD, was blocked by the mGluR-selective antagonist (+)-alpha-methyl-4-carboxyphenylglycine (+MCPG; 250 microM). +MCPG also blocked HFS-induced long-term potentiation (LTP) of the EPSP measured in the cell body. 6. These results suggest that (1S,3R)-ACPD-induced potentiation is NMDA receptor dependent, contrary to some previous findings, and provide further evidence that both synaptic and E-S potentiation induced by (1S,3R)-ACPD share common mechanisms of expression with HFS-induced LTP. The data emphasize the important role of mGluRs in induction of EPSP LTP and E-S potentiation.

Protective Effect of Ifenprodil Against Spreading Depression in the Mouse Entorhinal Cortex

2004 ◽  
Vol 92 (4) ◽  
pp. 2610-2614 ◽  
Author(s):  
Leonardo Coutinho Faria ◽  
Istvan Mody
Keyword(s):  
Nmda Receptor ◽  
Entorhinal Cortex ◽  
Spreading Depression ◽  
Ion Homeostasis ◽  
Brain Slices ◽  
Nmda Receptor Antagonist ◽  
Cerebrovascular Diseases ◽  
Nr2b Receptor Subunit ◽  
Nr2b Receptor

In the brain, spreading depression (SD) is characterized by a large extracellular DC shift, a massive failure of ion homeostasis and a transient cessation of neuronal function. Clinically, SD is believed to be involved in various neurological disorders including migraine and cerebrovascular diseases. The propagation of cortical SD requires the release of glutamate, and N-methyl-d-aspartate (NMDA) receptors play a crucial role in this process. Here, we have isolated the NMDA receptor-mediated component of extracellularly recorded field excitatory postsynaptic potentials (fEPSPs) in layers 2–3 of the entorhinal cortex of murine brain slices. In the absence of GABAA and AMPA receptor-mediated synaptic transmission, stimulation of layer 6 afferents every 15–90 s elicited spontaneous SD on average within 18.5 min after the start of the stimulation. In the presence of ifenprodil, an NR2B receptor subunit-selective NMDA receptor antagonist, the occurrence of SD was nearly abolished. Our results are consistent with an important role of NR2B subunits in triggering SD in the entorhinal cortex.

Role of AMPA/kainate receptors in transmission of the sympathetic baroreflex in rat CVLM

1997 ◽  
Vol 272 (3) ◽  
pp. R800-R812 ◽  
Author(s):  
T. Miyawaki ◽  
S. Suzuki ◽  
J. Minson ◽  
L. Arnolda ◽  
J. Chalmers ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Nmda Receptor Antagonist ◽  
Baroreceptor Reflex ◽  
Significant Inhibition ◽  
Kainate Receptors ◽  
Ventrolateral Medulla ◽  
Mk 801 ◽  
Aortic Nerve

We examined the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors within the caudal ventrolateral medulla (CVLM) in mediating the sympathetic baroreceptor reflex in anesthetized and paralyzed rats. Bilateral microinjection into CVLM of either DL-2-amino-5-phosphonovaleric acid [APV; a selective N-methyl-D-aspartic acid (NMDA) receptor antagonist, 20 mM, 100 nl] or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; a selective AMPA/kainate receptor antagonist, 2 mM, 100 nl) alone failed to eliminate the aortic nerve stimulation-evoked hypotension and inhibition of splanchnic sympathetic nerve activity (SNA) or the cardiac-related rhythmicity of SNA. All components of the sympathetic-baroreceptor reflex were abolished when kynurenate (100 mM, 30 nl) or mixtures of APV and CNQX (10 and 1 mM, respectively, 100 or 30 nl) were injected into CVLM. Injection of APV or CNQX into CVLM reduced aortic nerve-evoked inhibitory responses of bulbospinal sympathoexcitatory neurons in rostral ventrolateral medulla (RVLM). The extent of this reduction was variable. Usually, significant inhibition was preserved. In seven RVLM neurons, intravenous injection of MK-801 (NMDA receptor antagonist, 2 mg/kg) failed to eliminate aortic nerve-evoked inhibitory responses. However, inhibitory responses were abolished when CNQX was injected into CVLM after intravenous MK-801. We conclude that both NMDA and AMPA/kainate receptors in CVLM transmit baroreceptor information.

Role of the medullary lateral tegmental field in reflex-mediated sympathoexcitation in cats

2004 ◽  
Vol 286 (3) ◽  
pp. R451-R464 ◽  
Author(s):  
Hakan S. Orer ◽  
Gerard L. Gebber ◽  
Shaun W. Phillips ◽  
Susan M. Barman
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Sympathetic Nerve Activity ◽  
Nmda Receptor Antagonist ◽  
Vagal Afferents ◽  
Reflex Pathways ◽  
Excitatory Responses ◽  
Stimulation Of

We tested the hypothesis that blockade of N-methyl-d-aspartate (NMDA) and non-NMDA receptors on medullary lateral tegmental field (LTF) neurons would reduce the sympathoexcitatory responses elicited by electrical stimulation of vagal, trigeminal, and sciatic afferents, posterior hypothalamus, and midbrain periaqueductal gray as well as by activation of arterial chemoreceptors with intravenous NaCN. Bilateral microinjection of a non-NMDA receptor antagonist into LTF of urethane-anesthetized cats significantly decreased vagal afferent-evoked excitatory responses in inferior cardiac and vertebral nerves to 29 ± 8 and 24 ± 6% of control ( n = 7), respectively. Likewise, blockade of non-NMDA receptors significantly reduced chemoreceptor reflex-induced increases in inferior cardiac (from 210 ± 22 to 129 ± 13% of control; n = 4) and vertebral nerves (from 253 ± 41 to 154 ± 20% of control; n = 7) and mean arterial pressure (from 39 ± 7 to 21 ± 5 mmHg; n = 8). Microinjection of muscimol, but not an NMDA receptor antagonist, caused similar attenuation of these excitatory responses. Sympathoexcitatory responses to the other stimuli were not attenuated by microinjection of a non-NMDA receptor antagonist or muscimol into LTF. In fact, excitatory responses elicited by stimulation of trigeminal, and in some cases sciatic, afferents were enhanced. These data reveal two new roles for the LTF in control of sympathetic nerve activity in cats. One, LTF neurons are involved in mediating sympathoexcitation elicited by activation of vagal afferents and arterial chemoreceptors, primarily via activation of non-NMDA receptors. Two, non-NMDA receptor-mediated activation of other LTF neurons tonically suppresses transmission in trigeminal-sympathetic and sciatic-sympathetic reflex pathways.

Nicotine-induced anxiogenic-like behaviours of rats in the elevated plus-maze: possible role of NMDA receptors of the central amygdala

2011 ◽  
Vol 26 (4) ◽  
pp. 555-563 ◽  
Author(s):  
Mohammad Reza Zarrindast ◽  
Arash Aghamohammadi-Sereshki ◽  
Ameneh Rezayof ◽  
Parvin Rostami
Keyword(s):  
Locomotor Activity ◽  
Nmda Receptor ◽  
Nmda Receptors ◽  
Elevated Plus Maze ◽  
Nmda Receptor Antagonist ◽  
Central Amygdala ◽  
Receptor System ◽  
Plus Maze ◽  
Male Wistar Rats

The objective of the present study was to investigate the possible role of the N-methyl-D-aspartate (NMDA) receptor system of the central amygdala (CeA) in the anxiogenic-like effect of nicotine. Male Wistar rats with cannulas aimed to the CeA were submitted to the elevated plus-maze (EPM). Intraperitoneal (i.p.) injections of nicotine (0.6 and 0.8 mg/kg) decreased percentage open arm time spent (%OAT) and percentage open arm entries (%OAE), but not locomotor activity, indicating an anxiogenic-like response. Bilateral intra-CeA microinjection of NMDA (0.005–0.1 μ g/rat) decreased %OAT, but not %OAE and locomotor activity. Moreover, intra-CeA microinjection of NMDA (0.05 μ g) with an ineffective dose of nicotine (0.4 mg/kg, i.p.) reduced %OAT and %OAE without effect on locomotor activity. On the other hand, intra-CeA microinjection of the NMDA receptor antagonist D-AP5 (0.05–0.5 μ g/rat) increased both %OAT and %OAE, showing an anxiolytic-like effect of the drug. Co-administration of the same doses of D-AP5 with nicotine (0.6 mg/kg, i.p.) increased %OAT and %OAE, but not locomotor activity. Intra-CeA microinjection of D-AP5 reversed the response induced by NMDA (0.1 μ g/rat) in the EPM. The results may support the possible involvement of glutamate transmission, through NMDA receptors of central amygdala in the anxiogenic-like effect of nicotine in the EPM task.

scholarly journals Status Epilepticus Enhances Depotentiation after Fully Established LTP in an NMDAR-Dependent but GluN2B-Independent Manner

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xiati Guli ◽  
Tursonjan Tokay ◽  
Timo Kirschstein ◽  
Rüdiger Köhling
Keyword(s):  
Status Epilepticus ◽  
Nmda Receptor ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Nmda Receptor Antagonist ◽  
Independent Manner ◽  
Ca1 Neurons ◽  
Term Potentiation ◽  
Frequency Stimulation

N-Methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) can be reversed by low-frequency stimulation (LFS) referred to as depotentiation (DP). We previously found GluN2B upregulated in CA1 neurons from post-status epilepticus (post-SE) tissue associated with an enhanced LTP. Here, we tested whether LFS-induced DP is also altered in pathological GluN2B upregulation. Although LTP was enhanced in post-SE tissue, LTP was significantly reversed in this tissue, but not in controls. We next tested the effect of the GluN2B subunit-specific blocker Ro 25-6981 (1 μM) on LFS-DP. As expected, LFS had no effect on synaptic strength in the presence of the GluN2B blocker in control tissue. In marked contrast, LFS-DP was also attained in post-SE tissue indicating that GluN2B was obviously not involved in depotentiation. To test for NMDA receptor-dependence, we applied the NMDA receptor antagonist D-AP5 (50 μM) prior to LFS and observed that DP was abolished in both control and post-SE tissue confirming NMDA receptor involvement. These results indicate that control Schaffer collateral-CA1 synapses cannot be depotentiated after fully established LTP, but LFS was able to reverse LTP significantly in post-SE tissue. However, while LFS-DP clearly required NMDA receptor activation, GluN2B-containing NMDA receptors were not involved in this form of depotentiation.

scholarly journals NMDA Receptor Mediates the Anticonvulsant Effect of Hydroalcoholic Extract of Artemisia persica in PTZ-Induced Seizure in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Shakiba Nasiri-Boroujeni ◽  
Mohammad Rahimi-Madiseh ◽  
Zahra Lorigooini ◽  
Khadijeh Piroti ◽  
Mahmoud Rafieian-Koupaei ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Antioxidant Capacity ◽  
Nmda Receptor Antagonist ◽  
Seizure Threshold ◽  
Anticonvulsant Effect ◽  
Stress Effect ◽  
Hydroalcoholic Extract ◽  
Nmda Receptor Subunits ◽  
Antioxidative Stress

It is necessary to seek more effective sources to design new drug against epilepsy. This study aimed to evaluate the effect of hydroalcoholic extract of Artemisia persica on pentylenetetrazole- (PTZ-) induced seizure in male mice by investigating the possible role of the NMDA receptor and antioxidative stress effect. The phenolic profile of A. persica extract was determined by HPLC-DAD analysis. Mice were treated with normal saline or A. persica extract or pentobarbital or a subeffective dose of extract plus ketamine (NMDA receptor antagonist) and/or effective dose of extract plus NMDA. PTZ (90 mg/kg) was injected intravenously for induction of seizure. The seizure threshold was measured. Then mice were euthanized and the antioxidant capacity and the level of malondialdehyde (MDA) of the prefrontal cortex and serum were measured. The gene expression of NMDA receptor subunits (Nr2a and Nr2b) was determined by real-time PCR. Findings showed that A. persica extract increased the seizure threshold, increased antioxidant capacity, and decreased MDA levels in the serum and brain samples. A. persica extract reduced the expression of NMDA receptor subunits. The result showed that ketamine potentiated the effect of the subeffective dose of extract. HPLC analysis showed that quercetin had the highest flavonoid content and also caffeic acid had the highest content of the phenolic acids. A. persica extract probably via NMDA receptor exerts anticonvulsant properties.

Role of excitatory amino acids in mediating burst discharge of red nucleus neurons in the in vitro turtle brain stem-cerebellum

1991 ◽  
Vol 65 (3) ◽  
pp. 454-467 ◽  
Author(s):  
J. Keifer ◽  
J. C. Houk
Keyword(s):  
Spinal Cord ◽  
Amino Acid ◽  
Nmda Receptor ◽  
Excitatory Amino Acid ◽  
Red Nucleus ◽  
Nmda Receptor Antagonist ◽  
Excitatory Amino Acid Receptor ◽  
Bath Application

1. Bursts of discharge have been recorded in the red nucleus in several species and are thought to represent the expression of motor commands. A cerebellorubral circuit comprised of recurrent connections among the cerebellum, red nucleus, and reticular formation was postulated to function as a positive feedback loop that generates these motor commands and transmits them to the spinal cord via the rubrospinal pathway. We have used an in vitro preparation from the turtle that leaves the circuitry connecting the cerebellum, brain stem, and spinal cord intact to study the role of excitatory amino acid neurotransmitters and recurrent excitation in mediating the generation of burst discharges in the red nucleus. 2. Burst discharges were recorded extracellularly from single cells in the red nucleus in response to single pulse or brief train stimulation of the contralateral spinal cord or brief train stimuli applied to the ipsilateral cerebellar cortex. The firing characteristics and pharmacologic sensitivities of the bursts were independent of the type of stimulus used. The bursts had long durations ranging from 2 to 17 s and showed spike frequency adaptation. 3. Transection of the cerebellar peduncle, which eliminates inhibition impinging onto the cerebellorubral circuit, greatly enhanced the spontaneous activity and burst discharges recorded in the contralateral red nucleus. Furthermore, bath application of a solution containing elevated levels of calcium and magnesium blocked the expression of burst discharges even though synaptic activation of the neurons was not blocked. 4. The possibility that excitatory amino acid receptors mediate burst responses in the red nucleus was investigated in light of the antagonistic effects of elevated magnesium ions on bursting. Bath application of 100 microns DL-2-amino-5-phosphonovaleric acid (APV), a specific N-methyl-D-aspartate (NMDA) receptor antagonist; [10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)], a specific non-NMDA receptor antagonist; or 100 microM, DL-2-amino-4-phosphonobutyric acid (AP4), an agonist of a fourth class of excitatory amino acid receptor, blocked burst activity in the red nucleus. With a multibarreled pipette for simultaneous ejection of drug and recording, iontophoresis of APV or CNQX into the red nucleus blocked bursting whereas AP4 failed to show a significant effect. These data suggest that red nucleus neurons have both NMDA and non-NMDA receptors. The site of action of the AP4-sensitive receptor appears to be elsewhere in the cerebellorubral circuit. 5. Iontophoretic application of excitatory amino acid receptor agonists NMDA and quisqualate (Q) induced excitation of red nucleus neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

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