Антагонисты NMDA-рецепторов снижают чувствительность кожи при воздействии агониста TRPV1-рецепторов капсаицина

2021 ◽  
Vol 55 (9) ◽  
pp. 3-6
Author(s):  
Елена Анатольевна Иванова ◽  
Александр Иванович Матюшкин ◽  
Татьяна Александровна Воронина
Keyword(s):  
Mk 801

Глутаматные рецепторы широко представлены в центральной нервной системе и на периферии, что определяет их участие в центральной и периферической ноцицепции. В частности, NMDA-рецепторы локализованы в области дермоэпидермального соединения кожи. На иннервирующих кожу немиелинизированных нервных волокнах находятся TRPV1-рецепторы, способные функционально взаимодействовать с NMDA-рецепторами в каскадах кальций/кальмодулин-зависимой протеинкиназы типа II и протеинкиназы С. В данной работе оценено влияние неконкурентных антагонистов NMDA-рецепторов на периферическую сенситизацию кожи, вызванную подкожной инъекцией агониста TRPV1-рецепторов капсаицина, при разных способах введения. Установлено, что и высокоаффинный антагонист NMDA-рецепторов MK-801, и низкоаффинный антагонист NMDA-рецепторов гимантан снижают длительность реакции мышей на подкожную инъекцию раствора капсаицина в область плюсны при накожной аппликации, системном (внутрибрюшинном для гимантана и подкожном для МК-801) и подкожном интраплантарном введении.

Effect of MK-801 on sustained attention in rats

2011 ◽  
Author(s):  
I. M. Sukhanov ◽  
O. A. Dravolina ◽  
E. E. Zvartau ◽  
A. Y. Bespalov
Keyword(s):  
Sustained Attention ◽  
Mk 801

Clozapine Improves Behavioral and Biochemical Outcomes in a MK-801-Induced Mouse Model of Schizophrenia

2020 ◽  
Vol 39 (1) ◽  
pp. 1-12
Author(s):  
Syed Suhail Andrabi ◽  
Shruti Vishnoi ◽  
Riya Madan ◽  
Neha Bhardwaj ◽  
Heena Tabassum ◽  
...  
Keyword(s):  
Mouse Model ◽  
Mk 801

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.

scholarly journals In vivo glucose metabolism and glutamate levels in mGluR5 knockout mice: a multimodal neuroimaging study using [18F]FDG microPET and MRS

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yo-Han Joo ◽  
Yun-Kwan Kim ◽  
In-Gyu Choi ◽  
Hyeon-Jin Kim ◽  
Young-Don Son ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Glucose Metabolism ◽  
Cerebral Glucose Metabolism ◽  
Functional Coupling ◽  
Resonance Spectroscopy ◽  
Acute Administration ◽  
Multimodal Neuroimaging ◽  
Mk 801 ◽  
Genetic Ablation ◽  
Neuroimaging Study

Abstract Background Perturbed functional coupling between the metabotropic glutamate receptor-5 (mGluR5) and N-methyl-d-aspartate (NMDA) receptor-mediated excitatory glutamatergic neurotransmission may contribute to the pathophysiology of psychiatric disorders such as schizophrenia. We aimed to establish the functional interaction between mGluR5 and NMDA receptors in brain of mice with genetic ablation of the mGluR5. Methods We first measured the brain glutamate levels with magnetic resonance spectroscopy (MRS) in mGluR5 knockout (KO) and wild-type (WT) mice. Then, we assessed brain glucose metabolism with [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography before and after the acute administration of an NMDA antagonist, MK-801 (0.5 mg/kg), in the same mGluR5 KO and WT mice. Results Between-group comparisons showed no significant differences in [18F]FDG standardized uptake values (SUVs) in brain of mGluR5 KO and WT mice at baseline, but widespread reductions in mGluR5 KO mice compared to WT mice after MK-801 administration (p < 0.05). The baseline glutamate levels did not differ significantly between the two groups. However, there were significant negative correlations between baseline prefrontal glutamate levels and regional [18F]FDG SUVs in mGluR5 KO mice (p < 0.05), but no such correlations in WT mice. Fisher’s Z-transformation analysis revealed significant between-group differences in these correlations (p < 0.05). Conclusions This is the first multimodal neuroimaging study in mGluR5 KO mice and the first report on the association between cerebral glucose metabolism and glutamate levels in living rodents. The results indicate that mGluR5 KO mice respond to NMDA antagonism with reduced cerebral glucose metabolism, suggesting that mGluR5 transmission normally moderates the net effects of NMDA receptor antagonism on neuronal activity. The negative correlation between glutamate levels and glucose metabolism in mGluR5 KO mice at baseline may suggest an unmasking of an inhibitory component of the glutamatergic regulation of neuronal energy metabolism.

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