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 ◽  
...  

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.

1994 ◽  
Vol 267 (4) ◽  
pp. R1065-R1070 ◽  
Author(s):  
H. Ohta ◽  
W. T. Talman

In this study, we determined whether either N-methyl-D-aspartate (NMDA) receptors or non-NMDA receptors in the nucleus tractus solitarii (NTS) participate in the baroreceptor reflex in rats. Microinjection of an NMDA receptor antagonist, MK-801, and a non-NMDA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, into the NTS decreased the sensitivity of the baroreceptor reflex by 51 and 41%, respectively. Simultaneous administration of both agents further reduced the sensitivity of the baroreceptor reflex to 28% of control. A competitive NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid, also attenuated reflex bradycardia or tachycardia elicited by a single dose of phenylephrine or nitroprusside, respectively. Specificity of each antagonist's effects was supported by selective blockade of depressor responses produced by agonists that act at the NMDA and non-NMDA receptors, respectively. Results of this study indicate that both non-NMDA- and NMDA-sensitive receptors are involved in baroreceptor reflex transmission in the NTS.


2021 ◽  
Vol 15 ◽  
Author(s):  
Maria E. Plataki ◽  
Konstantinos Diskos ◽  
Christos Sougklakos ◽  
Marouso Velissariou ◽  
Alexandros Georgilis ◽  
...  

The neonatal MK-801 model of schizophrenia has been developed based on the neurodevelopmental and NMDA receptor hypofunction hypotheses of schizophrenia. This animal model is generated with the use of the NMDA receptor antagonist, MK-801, during different temporal windows of postnatal life of rodents leading to behavioral defects in adulthood. However, no studies have examined the role of specific postnatal time periods in the neonatal MK-801 (nMK-801) rodent model and the resulting behavioral and neurobiological effects. Thus, the goal of this study is to systematically investigate the role of NMDA hypofunction, during specific temporal windows in postnatal life on different cognitive and social behavioral paradigms, as well as various neurobiological effects during adulthood. Both female and male mice were injected intraperitoneally (i.p.) with MK-801 during postnatal days 7–14 (p7–14) or 11–15 (p11–15). Control mice were injected with saline during the respective time period. In adulthood, mice were tested in various cognitive and social behavioral tasks. Mice nMK-801-treated on p7–14 show impaired performance in the novel object, object-to-place, and temporal order object recognition (TOR) tasks, the sociability test, and contextual fear extinction. Mice nMK-801-treated on p11–15 only affects performance in the TOR task, the social memory test, and contextual fear extinction. No differences were identified in the expression of NMDA receptor subunits, the synapsin or PSD-95 proteins, either in the prefrontal cortex (PFC) or the hippocampus (HPC), brain regions significantly affected in schizophrenia. The number of parvalbumin (PV)-expressing cells is significantly reduced in the PFC, but not in the HPC, of nMK-801-treated mice on p7–14 compared to their controls. No differences in PV-expressing cells (PFC or HPC) were identified in nMK-801-treated mice on p11–15. We further examined PFC function by recording spontaneous activity in a solution that allows up state generation. We find that the frequency of up states is significantly reduced in both nMK-801-treated mice on p7–14 and p11–15 compared to saline-treated mice. Furthermore, we find adaptations in the gamma and high gamma activity in nMK-801-treated mice. In conclusion, our results show that MK-801 treatment during specific postnatal temporal windows has differential effects on cognitive and social behaviors, as well as on underlying neurobiological substrates.


1999 ◽  
Vol 276 (5) ◽  
pp. H1482-H1492 ◽  
Author(s):  
Wen-Bin Len ◽  
Julie Y. H. Chan

We investigated the role of glutamatergic projection from the parabrachial nucleus (PBN) complex to the rostral ventrolateral medulla (RVLM) in the PBN-induced suppression of reflex bradycardia in adult Sprague-Dawley rats that were maintained under pentobarbital anesthesia. Under stimulus conditions that did not appreciably alter the baseline systemic arterial pressure and heart rate, electrical (10-s train of 0.5-ms pulses, at 10–20 μA and 10–20 Hz) or chemical (l-glutamate, 1 nmol) stimulation of the ventrolateral regions and Köelliker-Fuse (KF) subnucleus of the PBN complex significantly suppressed the reflex bradycardia in response to transient hypertension evoked by phenylephrine (5 μg/kg iv). The PBN-induced suppression of reflex bradycardia was appreciably reversed by bilateral microinjection into the RVLM of the N-methyl-d-aspartate (NMDA)-receptor antagonist MK-801 (500 pmol) or the non-NMDA-receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (50 pmol). Anatomically, most of the retrogradely labeled neurons in the ventrolateral regions and KF subnucleus of the ipsilateral PBN complex after microinjection of fast blue into the RVLM were also immunoreactive to anti-glutamate antiserum. These results suggest that a direct glutamatergic projection to the RVLM from topographically distinct regions of the PBN complex may participate in the suppression of reflex bradycardia via activation of both NMDA and non-NMDA receptors at the RVLM.


2021 ◽  
Vol 22 (15) ◽  
pp. 8091
Author(s):  
Grace Jang ◽  
M. Bruce MacIver

Ketamine is a clinical anesthetic and antidepressant. Although ketamine is a known NMDA receptor antagonist, the mechanisms contributing to antidepression are unclear. This present study examined the loci and duration of ketamine’s actions, and the involvement of NMDA receptors. Local field potentials were recorded from the CA1 region of mouse hippocampal slices. Ketamine was tested at antidepressant and anesthetic concentrations. Effects of NMDA receptor antagonists APV and MK-801, GABA receptor antagonist bicuculline, and a potassium channel blocker TEA were also studied. Ketamine decreased population spike amplitudes during application, but a long-lasting increase in amplitudes was seen during washout. Bicuculline reversed the acute effects of ketamine, but the washout increase was not altered. This long-term increase was statistically significant, sustained for >2 h, and involved postsynaptic mechanisms. A similar effect was produced by MK-801, but was only partially evident with APV, demonstrating the importance of the NMDA receptor ion channel block. TEA also produced a lasting excitability increase, indicating a possible involvement of potassium channel block. This is this first report of a long-lasting increase in excitability following ketamine exposure. These results support a growing literature that increased GABA inhibition contributes to ketamine anesthesia, while increased excitatory transmission contributes to its antidepressant effects.


2005 ◽  
Vol 57 (1) ◽  
pp. 1-10
Author(s):  
Lidija Radenovic ◽  
Vesna Selakovic

The involvement of NMDA and AMPA/kainate receptors in the induction of superoxide production in the rat brain was examined after intrahippocampal injection of kainate, a non-NMDA receptor agonist; kainate plus CNQX, a selective AMPA/kainate receptor antagonist; or kainate plus APV, a selective NMDA receptor antagonist. The measurements took place at different times in the ipsi- and contralateral hippocampus, forebrain cortex, striatum, and cerebellum homogenates. The used glutamate antagonists both ensured sufficient neuroprotection in the sense of lowering superoxide production and raising MnSOD levels, but in the mechanisms and time dynamics of their effects were different. Our findings suggest that NMDA and AMPA/kainate receptors are differentially involved in superoxide production. <br><br><font color="red"><b> This article has been retracted. Link to the retraction <u><a href="http://dx.doi.org/10.2298/ABS150318026E">10.2298/ABS150318026E</a><u></b></font>


1993 ◽  
Vol 7 (4) ◽  
pp. 520-523 ◽  
Author(s):  
Hisao Komatsu ◽  
Junko Nogaya ◽  
Daisuke Anabuki ◽  
Kenji Ogli

1992 ◽  
Vol 4 (3) ◽  
pp. 221-222
Author(s):  
Yoram Shapira ◽  
Arthur M. Lam ◽  
Alan A. Artru ◽  
Ester Shohami

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