scholarly journals NMDA receptors on parvalbumin-positive interneurons and pyramidal neurons both contribute to MK-801 induced gamma oscillatory disturbances: Complex relationships with behaviour

2020 ◽  
Vol 134 ◽  
pp. 104625 ◽  
Author(s):  
Matthew R. Hudson ◽  
Elysia Sokolenko ◽  
Terence J. O'Brien ◽  
Nigel C. Jones
Keyword(s):  
Nmda Receptors ◽  
Pyramidal Neurons ◽  
Mk 801 ◽  
Complex Relationships

scholarly journals Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat

2021 ◽  
Author(s):  
Hong Wei ◽  
Zuyue Chen ◽  
Ari Koivisto ◽  
Antti Pertovaara
Keyword(s):  
Amino Acid ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Gap Junction ◽  
Male Rats ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Mk 801 ◽  
Mechanical Hypersensitivity ◽  
Pain Hypersensitivity

Abstract Background Earlier studies show that endogenous sphingolipids can induce pain hypersensitivity, activation of spinal astrocytes, release of proinflammatory cytokines and activation of TRPM3 channel. Here we studied whether the development of pain hypersensitivity induced by sphingolipids in the spinal cord can be prevented by pharmacological inhibition of potential downstream mechanisms that we hypothesized to include TRPM3, σ1 and NMDA receptors, gap junctions and D-amino acid oxidase. Methods Experiments were performed in adult male rats with a chronic intrathecal catheter for spinal drug administrations. Mechanical nociception was assessed with monofilaments and heat nociception with radiant heat. N,N-dimethylsphingosine (DMS) was administered to induce pain hypersensitivity. Ononetin, isosakuranetin, naringenin (TRPM3 antagonists), BD-1047 (σ1 receptor antagonist), carbenoxolone (a gap junction decoupler), MK-801 (NMDA receptor antagonist) and AS-057278 (inhibitor of D-amino acid oxidase, DAAO) were used to prevent the DMS-induced hypersensitivity, and pregnenolone sulphate (TRPM3 agonist) to recapitulate hypersensitivity. Results DMS alone produced within 15 min a dose-related mechanical hypersensitivity that lasted at least 24 h, without effect on heat nociception. Preemptive treatments with ononetin, isosakuranetin, naringenin, BD-1047, carbenoxolone, MK-801 or AS-057278 attenuated the development of the DMS-induced hypersensitivity, but had no effects when administered alone. Pregnenolone sulphate (TRPM3 agonist) alone induced a dose-related mechanical hypersensitivity that was prevented by ononetin, isosakuranetin and naringenin. Conclusions Among spinal pronociceptive mechanisms activated by DMS are TRPM3, gap junction coupling, the σ1 and NMDA receptors, and DAAO.

Role of N-methyl-D-aspartate receptors in the pontine pneumotaxic mechanism in the cat

1994 ◽  
Vol 76 (3) ◽  
pp. 1138-1143 ◽  
Author(s):  
L. Ling ◽  
D. R. Karius ◽  
D. F. Speck
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Partial Recovery ◽  
Inspiratory Time ◽  
Systemic Injection ◽  
Lung Inflation ◽  
Mk 801 ◽  
Efferent Limb ◽  
Adult Cats

Systemic injection of MK-801, an N-methyl-D-aspartate (NMDA) receptor-associated channel blocker, induces an apneusis in vagotomized cats similar to that produced by pontine respiratory group (PRG) lesions, suggesting the possible involvement of NMDA receptors in the pontine pneumotaxic mechanism. Previous results from our laboratory indicate that the efferent limb of the pontine pneumotaxic mechanism is unlikely to require NMDA receptor-mediated neurotransmission. Therefore, the present study examined the potential involvement of PRG NMDA receptors in the pontine pneumotaxic mechanism. Experiments were conducted in decerebrate, paralyzed, and ventilated adult cats. The effects on inspiratory time (TI) of MK-801 microinjection into PRG were tested in 12 cats. Pressure microinjection of MK-801 (15 mM, 80–3,000 nl) significantly prolonged TI in all animals when lung inflation was withheld. TI progressively increased in most animals for > or = 30 min. After this period, partial recovery of the effect occurred in eight cats as TI shortened toward predrug levels. In three animals, microinjection of MK-801 induced a complete apneusis in the absence of lung inflation from which there was no detectable recovery. Microinjections into regions approximately 2 mm distant from PRG produced little or no effect. These results provide evidence that NMDA receptors located in the region of PRG play an important functional role in the control of the breathing cycle.

scholarly journals Exposure to cyclic intermittent hypoxia increases expression of functional NMDA receptors in the rat carotid body

2009 ◽  
Vol 106 (1) ◽  
pp. 259-267 ◽  
Author(s):  
Yuzhen Liu ◽  
En-Sheng Ji ◽  
Shuanglin Xiang ◽  
Renaud Tamisier ◽  
Jingli Tong ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Acute Hypoxia ◽  
Sprague Dawley ◽  
Excitatory Neurotransmitter ◽  
Mk 801 ◽  
Baseline Activity ◽  
Nmda Receptor Blocker

Although large quantities of glutamate are found in the carotid body, to date this excitatory neurotransmitter has not been assigned a role in chemoreception. To examine the possibility that glutamate and its N-methyl-d-aspartate (NMDA) receptors play a role in acclimatization after exposure to cyclic intermittent hypoxia (CIH), we exposed male Sprague-Dawley rats to cyclic hypoxia or to room air sham (Sham) for 8 h/day for 3 wk. Using RT-PCR, Western blot analysis, and immunohistochemistry, we found that ionotropic NMDA receptors, including NMDAR1, NMDAR2A, NMDAR2A/2B, are strongly expressed in the carotid body and colocalize with tyrosine hydroxylase in glomus cells. CIH exposure enhanced the expression of NMDAR1 and NMDAR2A/2B but did not substantially change the level of NMDAR2A. We assessed in vivo carotid sinus nerve activity (CSNA) at baseline, in response to acute hypoxia, in response to infused NMDA, and in response to infused endothelin-1 (ET-1) with and without MK-801, an NMDA receptor blocker. Infusion of NMDA augmented CSNA in CIH rats (124.61 ± 2.64% of baseline) but not in sham-exposed rats. Administration of MK-801 did not alter baseline activity or response to acute hypoxia, in either CIH or sham animals but did reduce the effect of ET-1 infusion on CSNA (CSNA after ET-1 = 160.96 ± 8.05% of baseline; ET-1 after MK-801 = 118.56 ± 9.12%). We conclude that 3-wk CIH exposure increases expression of NMDA functional receptors in rats, suggesting glutamate and its receptors may play a role in hypoxic acclimatization to CIH.

scholarly journals NMDA receptors mediate peripheral chemoreceptor afferent input in the conscious rat

1998 ◽  
Vol 84 (3) ◽  
pp. 853-861 ◽  
Author(s):  
Patricia J. Ohtake ◽  
José E. Torres ◽  
Yair M. Gozal ◽  
Gavin R. Graff ◽  
David Gozal
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Receptor Activation ◽  
Sodium Cyanide ◽  
Respiratory Drive ◽  
Peripheral Chemoreceptor ◽  
Cardiorespiratory Control ◽  
Mk 801 ◽  
Ventilatory Responses ◽  
Before And After

N-methyl-d-aspartate (NMDA) glutamate receptors mediate critical components of cardiorespiratory control in anesthetized animals. The role of NMDA receptors in the ventilatory responses to peripheral and central chemoreceptor stimulation was investigated in conscious, freely behaving rats. Minute ventilation (V˙e) responses to 10% O2, 5% CO2, and increasing intravenous doses of sodium cyanide were measured in intact rats before and after intravenous administration of the NMDA receptor antagonist MK-801 (3 mg/kg). After MK-801, eupcapnic tidal volume (Vt) decreased while frequency increased, resulting in a modest reduction inV˙e. Inspiratory time (Ti) decreased, whereas expiratory time remained unchanged. TheV˙e responses to hypercapnia were qualitatively similar in control and MK-801 conditions, with slight reductions in respiratory drive (Vt/Ti) after MK-801. In contrast, responses to hypoxia were markedly attenuated after MK-801 and were primarily due to reduced frequency changes, whereas Vt was unaffected. Sodium cyanide doses associated with significantV˙eincreases were 5 and 50 μg/kg before and after MK-801, respectively. Thus 1-log shift to the right of individual dose-response curves occurred with MK-801. Selective carotid body denervation reducedV˙e during hypoxia by 70%, and residual hypoxic ventilatory responses were abolished after MK-801. These findings suggest that, in conscious rats, carotid and other peripheral chemoreceptor-mediated hypoxic ventilatory responses are critically dependent on NMDA receptor activation and that NMDA receptor mechanisms are only modestly involved during hypercapnia.

ACTH binds to [3H]MK-801-labelled rat hippocampal NMDA receptors

1992 ◽  
Vol 226 (4) ◽  
pp. 377-379 ◽  
Author(s):  
R.R. Trifiletti ◽  
M.R. Pranzatelli
Keyword(s):  
Nmda Receptors ◽  
Mk 801

Blockade of NMDA receptors by MK-801 reverses the changes in striatal glutamate immunolabeling in 6-OHDA-lesioned rats

Synapse ◽  
2001 ◽  
Vol 42 (1) ◽  
pp. 54-61 ◽  
Author(s):  
Siobhan Robinson ◽  
Lisa Krentz ◽  
Cynthia Moore ◽  
Charles K. Meshul
Keyword(s):  
Nmda Receptors ◽  
Mk 801

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

2006 ◽  
Vol 290 (3) ◽  
pp. R642-R651 ◽  
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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