Both NMDA and non-NMDA receptors in the NTS participate in the baroreceptor reflex in rats

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.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.272.3.r800 ◽

1997 ◽

Vol 272 (3) ◽

pp. R800-R812 ◽

Cited By ~ 5

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.

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Hindbrain administration of NMDA receptor antagonist AP-5 increases food intake in the rat

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00641.2005 ◽

2006 ◽

Vol 290 (3) ◽

pp. R642-R651 ◽

Cited By ~ 19

Author(s):

Chun-Yi Hung ◽

M. Covasa ◽

R. C. Ritter ◽

G. A. Burns

Keyword(s):

Nmda Receptor ◽

Food Intake ◽

Nmda Receptors ◽

Receptor Antagonist ◽

Intraperitoneal Injection ◽

Sucrose Solution ◽

Nmda Receptor Antagonist ◽

Saline Control ◽

Sucrose Intake ◽

Mk 801

Hindbrain administration of MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) channel blocker, increases meal size, suggesting NMDA receptors in this location participate in control of food intake. However, dizocilpine (MK-801) reportedly antagonizes some non-NMDA ion channels. Therefore, to further assess hindbrain NMDA receptor participation in food intake control, we measured deprivation-induced intakes of 15% sucrose solution or rat chow after intraperitoneal injection of either saline vehicle or d(-)-2-amino-5-phosphonopentanoic acid (AP5), a competitive NMDA receptor antagonist, to the fourth ventricular, or nucleus of the solitary tract (NTS). Intraperitoneal injection of AP5 (0.05, 0.1, 1.0, 3.0, and 5.0 mg/kg) did not alter 30-min sucrose intake at any dose (10.7 ± 0.4 ml, saline control) (11.0 ± 0.8, 11.2 ± 1.0, 11.2 ± 1.0, 13.1 ± 2.2, and 11.0 ± 1.9 ml, AP5 doses, respectively). Fourth ventricular administration of both 0.2 μg (16.7 ± 0.6 ml) and 0.4 μg (14.9 ± 0.5 ml) but not 0.1 and 0.6 μg of AP5 significantly increased 60-min sucrose intake compared with saline (11.2 ± 0.4 ml). Twenty-four hour chow intake also was increased compared with saline (AP5: 31.5 ± 0.1 g vs. saline: 27.1 ± 0.6 g). Furthermore, rats did not increase intake of 0.2% saccharin after fourth ventricular AP5 administration (AP5: 9.8 ± 0.7ml, vs. saline: 10.5 ± 0.5ml). Finally, NTS AP5 (20 ng/30 nl) significantly increased 30- (AP5: 17.2 ± 0.7 ml vs. saline: 14.6 ± 1.7 ml), and 60-min (AP5: 19.4 ± 0.6 ml vs. saline: 15.5 ± 1.4 ml) sucrose intake, as well as 24-h chow intake (AP5: 31.6 ± 0.3 g vs. saline: 26.1 ± 1.2 g). These results support the hypothesis that hindbrain NMDA receptors participate in control of food intake and suggest that this participation also may contribute to control of body weight over a 24-h period.

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Trigeminal Expression of N-Methyl-D-Aspartate Receptor Subunit 1 and Behavior Responses to Experimental Tooth Movement in Rats

The Angle Orthodontist ◽

10.2319/082308-444.1 ◽

2009 ◽

Vol 79 (5) ◽

pp. 951-957 ◽

Cited By ~ 10

Author(s):

Zhi Yang ◽

Yan Wang ◽

Wei Luo ◽

Xiaochuan Hua ◽

Peter Wamalwa ◽

...

Keyword(s):

Nmda Receptor ◽

Nmda Receptors ◽

Receptor Antagonist ◽

Tooth Movement ◽

Movement Time ◽

Nmda Receptor Antagonist ◽

Mk 801 ◽

Nocifensive Behavior ◽

Force Magnitude ◽

Experimental Tooth Movement

Abstract Objective: To test the hypothesis that peripheral N-methyl-D-aspartate (NMDA) receptors play a role in pain induced by experimental tooth movement. Materials and Methods: Male Sprague-Dawley rats weighing between 200 g and 300 g were used in this study. Expression of NMDA receptors subunit 1 (NMDAR1) in the mandibular portion of the trigeminal ganglion (TG) was determined by Western blotting 4 hours and 1, 2, 3, 5, 7, and 14 days after tooth movement. Changes in the time taken by the rats on nocifensive behavior then effects of NMDA receptor antagonist MK-801 and force magnitude on these changes in behavior and NMDAR1 expression were evaluated. Results: Experimental tooth movement led to a statistically significant increase in NMDAR1 expression at protein level from day 1 to 7 after force application initiating tooth movement. Time spent on nocifensive behavior dramatically increased from day 1 to 7. The rhythm in NMDAR1 expression in the TG and behavioral activities correlated well with the initial orthodontic pain responses. The magnitude of the nocifensive behavior and NMDAR1 expression were both force magnitude dependent and could be reduced by peripheral NMDA receptor antagonist MK-801. Conclusions: The hypothesis is accepted. Peripheral NMDA receptors are modulated by experimental tooth movement and involved in the development of tooth movement pain.

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Regionally different responses of GABAergic interneuron populations to a NMDA receptor antagonist challenge with MK-801 and an antipsychotic “rescue therapy“ in an animal model of psychosis

Pharmacopsychiatry ◽

10.1055/s-2007-991763 ◽

2007 ◽

Vol 40 (05) ◽

Author(s):

J Genius ◽

I Braun ◽

H Grunze ◽

J Benninghoff ◽

HJ Möller ◽

...

Keyword(s):

Animal Model ◽

Nmda Receptor ◽

Receptor Antagonist ◽

Rescue Therapy ◽

Nmda Receptor Antagonist ◽

Gabaergic Interneuron ◽

Mk 801

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Disturbed alpha and gamma oscillations ex vivo after single application of the NMDA receptor antagonist MK-801

10.26226/morressier.5785edccd462b80296c98efe ◽

2016 ◽

Author(s):

Zoltan Gerevich

Keyword(s):

Nmda Receptor ◽

Receptor Antagonist ◽

Ex Vivo ◽

Gamma Oscillations ◽

Nmda Receptor Antagonist ◽

Single Application ◽

Mk 801

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Ketamine Produces a Long-Lasting Enhancement of CA1 Neuron Excitability

International Journal of Molecular Sciences ◽

10.3390/ijms22158091 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8091

Author(s):

Grace Jang ◽

M. Bruce MacIver

Keyword(s):

Nmda Receptor ◽

Potassium Channel ◽

Receptor Antagonist ◽

Hippocampal Slices ◽

Nmda Receptor Antagonist ◽

Channel Block ◽

Mk 801 ◽

Ca1 Region ◽

Excitatory Transmission ◽

Ketamine Anesthesia

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.

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Reduction of food intake by cholecystokinin requires activation of hindbrain NMDA-type glutamate receptors

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00026.2011 ◽

2011 ◽

Vol 301 (2) ◽

pp. R448-R455 ◽

Cited By ~ 25

Author(s):

Jason Wright ◽

Carlos Campos ◽

Thiebaut Herzog ◽

Mihai Covasa ◽

Krzysztof Czaja ◽

...

Keyword(s):

Nmda Receptor ◽

Food Intake ◽

Nmda Receptors ◽

Receptor Antagonist ◽

Fourth Ventricle ◽

Nmda Receptor Antagonist ◽

Behavioral Pattern ◽

Vagal Afferents ◽

Nmda Receptor Antagonists ◽

The Brain

Intraperitoneal injection of CCK reduces food intake and triggers a behavioral pattern similar to natural satiation. Reduction of food intake by CCK is mediated by vagal afferents that innervate the stomach and small intestine. These afferents synapse in the hindbrain nucleus of the solitary tract (NTS) where gastrointestinal satiation signals are processed. Previously, we demonstrated that intraperitoneal (IP) administration of either competitive or noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists attenuates reduction of food intake by CCK. However, because vagal afferents themselves express NMDA receptors at both central and peripheral endings, our results did not speak to the question of whether NMDA receptors in the brain play an essential role in reduction of feeding by CCK. We hypothesized that activation of NMDA receptors in the NTS is necessary for reduction of food intake by CCK. To test this hypothesis, we measured food intake following IP CCK, subsequent to NMDA receptor antagonist injections into the fourth ventricle, directly into the NTS or subcutaneously. We found that either fourth-ventricle or NTS injection of the noncompetitive NMDA receptor antagonist MK-801 was sufficient to inhibit CCK-induced reduction of feeding, while the same antagonist doses injected subcutaneously did not. Similarly fourth ventricle injection of d-3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphoric acid (d-CPPene), a competitive NMDA receptor antagonist, also blocked reduction of food intake following IP CCK. Finally, d-CPPene injected into the fourth ventricle attenuated CCK-induced expression of nuclear c-Fos immunoreactivity in the dorsal vagal complex. We conclude that activation of NMDA receptors in the hindbrain is necessary for the reduction of food intake by CCK. Hindbrain NMDA receptors could comprise a critical avenue for control and modulation of satiation signals to influence food intake and energy balance.

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