1.Change of neurocytes in acute intoxicated encephalopathy induced by 1, 2-dichloroethane after intervention with antagonists.
Jing WANG ; Mao-Long GAO ; Ying-Tao SHI ; Qiao NIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2007;25(12):726-729
OBJECTIVETo study the role of N-methyl-D-aspartate receptor and Ca(2+) in acute intoxicated encephalopathy induced by 1, 2-dichloroethane (1, 2-DCE) in vitro.
METHODSNeurocytes of new born rats were cultured in vitro, which were administered with different doses of 1, 2-DCE, and NMDAR and Ca(2+) antagonists including Ketamine and Nimodiping respectively. The cell morphologic structures were observed under light microscope, and its proliferation was detected by Cell Counting Kit-VIII.
RESULTS1, 2-DCE could damage the normal morphological structure of neurocytes: the cell body swelled and broke down, the karyon slurred or disappeared, the axone became shorten and thick, connection of neurocytes was reduced, the cell membrane was half-baked, injury of neurocytes became severer with the increase of the dose of 1, 2-DCE. There was no statistical difference in the proliferation of neurocytes between every 1, 2-DCE groups (P > 0.05), but there was significantly statistical difference between 1, 2-DCE groups, the control group, and the retarder groups (P < 0.01).
CONCLUSION1, 2-DCE can damage the normal morphological structure of neurocytes, and the damage will become severer with the increase of the dose of 1, 2-DCE. However, the cell morphologic structures and proliferation of antagonist groups are much better than those in the 1, 2-DCE groups.
Animals ; Calcium ; antagonists & inhibitors ; physiology ; Cells, Cultured ; Ethylene Dichlorides ; toxicity ; Neurons ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; antagonists & inhibitors ; physiology
2.Synaptic and molecular mechanisms of glutamatergic synapses in pain and memory.
Acta Physiologica Sinica 2003;55(1):1-8
Glutamate is a fast excitatory transmitter in mammalian brains. Glutamatergic synapses are found in central regions related to pain transmission, plasticity and modulation. Glutamate NMDA receptors in forebrain structures are well known to contribute to the formation and storage of information. Here we propose the hypothesis that forebrain NMDA receptors play an important role in persistent inflammatory pain by re-enforcing glutamate sensory transmission in the brain. Mice with enhanced function of forebrain NMDA receptors demonstrate selective enhancement of persistent pain and allodynia. Drugs targeting forebrain NMDA NR2B receptors may serve as a new class of medicine to control persistent pain in humans.
Animals
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Brain
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metabolism
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physiology
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Glutamic Acid
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physiology
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Humans
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Memory
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physiology
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Mice
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Pain
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drug therapy
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physiopathology
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Receptors, Glutamate
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drug effects
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physiology
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Receptors, N-Methyl-D-Aspartate
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drug effects
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metabolism
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Synapses
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physiology
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Synaptic Transmission
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physiology
3.Effects of ginkgo biloba extracts on NMDA-activated currents in acutely isolated rat hippocampal neurons.
Shao LI ; Chang-Kai SUN ; Xin-Cai JI ; Jian ZHANG
Chinese Journal of Applied Physiology 2007;23(3):305-308
AIMTo investigate effect of ginkgo biloba extract (GBE) on N-methyl-D-aspartate (NMDA)-activated currents (I(NMDA)) and evaluate further the modulatory effects of Micro-GBE/Nano-GBE.
METHODSBy means of whole-cell patch clamp technique, NMDA-activated currents from acutely isolated rat hippocampal neurons were recored.
RESULTSThe majority of the neurons examined (81.8%, 90/110) were sensitive to NMDA (1 mmol/L) and its co-agonist Gly (10 micromol/L). NMDA activated an inward current, which manifested apparent desensitization and could be blocked by its specific antagonist MK-801. After the neurons were treated with Micro/Nano GBE (0.1 mg/ml) followed by the application of NMDA (1 mmol/L) and Gly (10 micromol/L) for 30 s, it was show that NMDA-activated currents were obviously inhibited (P < 0.01, n = 8). The inhibitory rate were 40% +/- 17% and 64% +/- 15% respectively. It showed that the modulatory effect of Nano-GBE (dissolved in the stander extracellular solution) on NMDA-activated current was significantly higher than that of Micro-GBE (dissolved in DMSO) (P < 0.05).
CONCLUSIONThe inward currents activated by NMDA could be depressed by Micro-GBE and Nano-GBE. The modulatory effects of GBE on NMDA-activated current are expected to contribute to the neuroprotective effects of ginkgo biloba extracts. In addition, at the same concentration, the modulatory effect of Nano-GBE on NMDA-activated current is better than that of Micro-GBE.
Animals ; Cells, Cultured ; Ginkgo biloba ; Hippocampus ; drug effects ; physiology ; N-Methylaspartate ; pharmacology ; Neurons ; drug effects ; physiology ; Patch-Clamp Techniques ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; drug effects
4.Relation between adenosine A1 receptor and NMDA receptor on synaptic transmission in dentate gyrus of hippocampus.
Dan-shen ZHANG ; Lei-ming REN ; Li ZHANG
Acta Pharmaceutica Sinica 2004;39(4):245-249
AIMTo observe the effect of adenosine A, receptor antagonist on synaptic transmission in the dentate gyrus of hippocampus and its relations with NMDA receptor.
METHODSUsing electrophysiological technique to record the long-term potentiation (LTP), the relation between selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and NMDA receptor agonist/antagonist, in both basic synaptic transmission and 200 Hz high-frequency stimulation (HFS) induced LTP of the dentate gyrus of hippocampus in anesthetized rats, was studied.
RESULTSDPCPX (6 mg x L(-1), 5 microL, icv) or NMDA (0.2 mg x L(-1), 5 microL, icv) was shown not to affect the synaptic transmission in the dentate gyrus in rats. DPCPX was found not to affect the keeping of LTP induced by HFS after icv NMDA. But the basic synaptic transmission and the magnitude of LTP induced by HFS in the dentate gyrus after icv NMDA could be enhanced significantly by icv DPCPX in advance. DPCPX could not affect the magnitude of LTP inhibited by AP5 (0.5 mg x L(-1), 5 microL) NMDA receptor antagonist, but the inhibitory effect of AP5 on LTP could be antagonized by icv DPCPX in advance.
CONCLUSIONThe selective adenosine A1 receptor antagonist DPCPX could not affect the synaptic transmission in the dentate gyrus of hippocampus, but could significantly enhance the effect of NMDA receptor in both basic synaptic transmission and HFS induced LTP in the dentate gyrus of hippocampus in anesthetized rats.
2-Amino-5-phosphonovalerate ; pharmacology ; Adenosine A1 Receptor Antagonists ; Animals ; Dentate Gyrus ; drug effects ; physiology ; Long-Term Potentiation ; drug effects ; Male ; N-Methylaspartate ; pharmacology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate ; antagonists & inhibitors ; Synaptic Transmission ; drug effects ; Xanthines ; pharmacology
5.Inhibitory effect of interleukin-6 on NMDA-stimulated neuronal firing activity and possible mechanism involved in the effect.
Xian-Feng ZHAN ; Bing LI ; Bei WU ; Yu-Ping PENG ; Yi-Hua QIU
Chinese Journal of Applied Physiology 2010;26(3):365-369
OBJECTIVETo study the effect and the possible mechanism of IL-6 on NMDA-excited neuronal discharges of rats in vitro.
METHODSThe cerebellar slices were prepared and spontaneous discharges of single cerebellar interposed nuclear (IN) neurons were recorded by extracellular recordings. The cerebellar slices were perfused with artificial cerebral spinal fluid (ACSF) containing N-methyl-D-aspartate (NMDA), IL-6, JAK inhibitor AG490. The changes in firing activities of the neurons treated with the drugs were recorded. The levels of phosphorylation at serine 897 site of NMDA receptor subunit 1 (NR1) in the neurons treated with various drugs mentioned above were detected by Western blot.
RESULTSThe discharge rates of the neurons that were treated with IL-6 together with NMDA were significantly lower than those of the neurons treated with NMDA alone. AG490 partially blocked the inhibitory effect of IL-6 on the NMDA-stimulated neuronal firing activity. The treatment of the neurons with IL6 and NMDA led to a concentration-dependent suppression of the phospho-NR1 expression relative to those neurons treated with NMDA alone. AG490 blocked the effect of the IL-6-induced depression of phospho-NR1 expression.
CONCLUSIONIL-6 inhibits NMDA-stimulated neuronal firing activity, and simultaneously down-regulates the phosphorylation of NR1 at serine 897 site.
Animals ; Cerebellum ; drug effects ; metabolism ; In Vitro Techniques ; Interleukin-6 ; pharmacology ; N-Methylaspartate ; pharmacology ; Nerve Growth Factors ; metabolism ; Neurons ; drug effects ; metabolism ; physiology ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism
6.Role of phospho-calcium/ calmodulin-dependent protein kinase II in the induction and maintenance of long-term potentiation of C-fiber-evoked field potentials in spinal dorsal horn of the rat.
Wen-Jun XIN ; Ming-Tao LI ; Hong-Wei YANG ; Hong-Mei ZHANG ; Neng-Wei HU ; Xiao-Dong HU ; Tong ZHANG ; Xian-Guo LIU
Acta Physiologica Sinica 2004;56(1):83-88
Our previous studies have shown that long-term potentiation (LTP) of C-fiber-evoked field potentials in the spinal dorsal horn is NMDA receptor dependent. It is known that elevation of Ca(2+) in the postsynaptic neurons through NMDA receptor channels during high-frequency stimulation of the afferent fibers is crucial for LTP induction, but how this leads to a prolonged potentiation of synaptic transmission in the spinal dorsal horn is not clear. In the hippocampus, a rise of Ca(2+) activates calcium/calmodulin-dependent protein kinase II (CaMK II) through autophosphorylation. Once this occurs, the kinase remains active, even when Ca(2+) concentration returns to baseline level. Phosphorylated CaMK II potentiates synaptic transmission by enhancement of AMPA receptor channel function via phosphorylation of GluR1 subunit of the receptor and the addition of AMPA receptors to synapses. Up to now, the role of CaMK II in the induction and maintenance of LTP of the C-fiber-evoked field potentials in spinal dorsal horn has not been evaluated. In the present study, we examined the expression of CaMK II and phospho-CaMK II in the lumbar segments (L4-L6) of the rat spinal dorsal horn at 30 min and 3 h after the establishment of LTP induced by tetanic electrical stimulation of the sciatic nerve (40 V, 0.5 ms pulses at 100 Hz for 1 s repeated four times at 10 s intervals) by using Western blot and electrophysiological techniques. To determine the role of the phospho-CaMK II in the induction and maintenance of the spinal LTP, a selective CaMK II inhibitor KN-93 (100 micromol/L) was applied directly onto the spinal cord at the recording segments before and after LTP induction. We found that (1) the protein level of phospho-CaMKII increased at both 30 min and 3 h after LTP induction, while the total protein level of CaMK II increased at 3 h but not at 30 min after LTP induction. (2) Spinal application of KN-93 at 30 min prior to the tetanus blocked both LTP induction and the increase in phospho-CaMK II. (3) 30 min after LTP induction, spinal application of KN-93 depressed LTP and the level of phospho-CaMK II (n=3). (4) Spinal application of KN-93 at 3 h after LTP, however, affected neither the amplitude of the spinal LTP nor the level of phospho-CaMK II in the spinal dorsal horn. These results suggest that activation of CaMK II is probably crucial for the induction and the early-phase maintenance of LTP of C-fiber-evoked field potentials in the spinal dorsal horn.
Animals
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Evoked Potentials
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Long-Term Potentiation
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physiology
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Male
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Nerve Fibers, Unmyelinated
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physiology
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Neural Pathways
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drug effects
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physiology
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Phosphoprotein Phosphatases
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metabolism
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Phosphorylation
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Posterior Horn Cells
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enzymology
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physiology
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate
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Spinal Cord
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enzymology
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physiology
7.The effects of sodium salicylate on the expression of GABAalpha, NR1 and hearing response properties of inferior colliculus neurons in mice.
Shi-Hua YIN ; Shu-Sheng GONG ; Kai-Sheng YAN ; Sui LI ; Pei CHEN ; Guang Li CHEN
Chinese Journal of Applied Physiology 2006;22(2):200-205
AIMTo study the effects of sodium salicylate on the expression of GABAalpha NR1 and hearing response properties of inferior colliculus neurons in mice.
METHODSThirty-six kunming mice were divided into three groups (A, B, C,). The expression of GABAalpha NR1 were measured by using RT-PCR. The intensity-rates functions, intensity-latency functions and frequency-turning curves were recorded by extracellular electrophysiological recording techniques.
RESULTS(1) The expression of GABAalpha mRNA of B group was decreased remarkably than the control group (A group, P < 0.05), there weren't noticeable differences between A group and C group (P > 0.05). The expression of NR1 mRNA of B group was increased remarkably than the control group (A group, P < 0.01), there were noticeable differences between A group and C group P < 0.05). (2) The intensity-rates functions, intensity-latency functions were monotonic while the frequency-turning curves were more broad when sodium salicylate was given. (3) The intensity-rates functions, intensity-latency functions were non-monotonic while the frequency-turning curves were sharpened after lidocaine was given.
CONCLUSIONS(1) The results suggested that administration of sodium salicylate decreased the expression of GABAalpha while increased the expression of NR1mRNA. (2) The intensity-rates functions, intensity-latency functions were monotonic, the frequency-turning curves were more broad when salicylate was given and the changes above could be reversed by given lidocaine.
Acoustic Stimulation ; Animals ; Inferior Colliculi ; drug effects ; metabolism ; physiology ; Mice ; Mice, Inbred Strains ; Neurons ; drug effects ; metabolism ; physiology ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Sodium Salicylate ; pharmacology ; gamma-Aminobutyric Acid ; metabolism
8.Effect of glycine site/NMDA receptor antagonist MRZ2/576 on the conditioned place preference and locomotor activity induced by morphine in mice.
Yong-ping ZHU ; Zai-hao LONG ; Ming-lan ZHENG ; Ralf BINSACK
Journal of Zhejiang University. Science. B 2006;7(12):998-1005
OBJECTIVETo study the effect of glycine site/NMDA (N-methyl-D-aspartate) receptor antagonist MRZ2/576 on the conditioned place preference (CPP) and locomotor activity induced by morphine in mice.
METHODSDifferent doses (1.25, 2.5 and 5 mg/kg, i.p.) of MRZ2/576 were used to evaluate the effect of MRZ2/576 on the acquisition and expression of CPP induced by morphine (5 mg/kg) in mice. In addition, we examined the locomotor activity of mice in conditioning and testing phase of CPP paradigm.
RESULTSMRZ2/576 alone could not establish place preference, but a 5 mg/kg dose of MRZ2/576 could block both acquisition and expression of morphine-induced CPP. In testing phase of CPP, there was no statistical difference for locomotor activity between the groups; injection of MRZ2/576 showed a dose-dependent decrease of locomotor activity on both control and morphine-treated mice, especially 5 mg/kg of MRZ2/576 significantly suppressed the locomotor activity of mice.
CONCLUSIONBased on the present results, we assume that MRZ2/576 can antagonize the rewarding effect of morphine, suggesting that this glycine site/NMDA receptor antagonist could be used to treat addictions due to its light side effect profile.
Animals ; Conditioning (Psychology) ; drug effects ; Excitatory Amino Acid Antagonists ; pharmacology ; Magnesium ; physiology ; Male ; Mice ; Mice, Inbred ICR ; Morphine ; pharmacology ; Motor Activity ; drug effects ; Phthalazines ; pharmacology ; Receptors, N-Methyl-D-Aspartate ; antagonists & inhibitors
9.Effects of agmatine on the electrical activity of subfornical organ neurons.
Ze-Min WANG ; Shu-Mei JI ; Hao ZHANG ; Guang-Qi SUN ; Zhi-An WANG ; Rui-Rong HE
Acta Physiologica Sinica 2004;56(4):493-497
The aim of this study was to investigate the effects of agmatine (Agm) on the electrical activity of neurons in subfornical organ (SFO) slices using extracellular recording technique. The results are as follows. (1) In response to the application of Agm (1.0 micromol/L) into the superfusate for 2 min, the discharge rate of 24/28 (85.7%) subfornical neurons was decreased significantly, while the discharge rate of 4/28 (14.3%) neurons were not affected. (2) Pretreatment with L-glutamate (0.3 mmol/L) led to a marked increase in the discharge rate of 19/24 (79.2%) subfornical neurons in an epileptiform pattern and the activity of the remaining 5/24 (20.8%) neurons was unaffected. By application of Agm (1.0 micromol/L) into the superfusate for 2 min, the epileptiform dicharge of 15/19 (78.9%) neurons was suppressed significantly, while that of the other 4 (21.1%) neurons was not inhibited. (3) In 12 neurons, perfusion of the selective L-type calcium channel agonist, Bay K-8644 (0.1 micromol/L), induced a significant increase in the discharge rate of 10/12 (83.3%) neurons, while the other 2 (16.7%) neurons showed no change. The increased discharge of 8/10 (80%) neurons was reduced by application of Agm (1.0 micromol/L) into the superfusate and that of 2/10 (20%) neurons was not affected. (4) Application of nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 50 micromol/L) into the superfusate also significantly increased the discharge rate of 6/9 (66.7%) neurons, and that of 3/9 (33.3%) neurons had no response. Agm (1.0 micromol/L) applied into the superfusate reduced the increased discharge of all 6/6 (100%) neurons. These results suggest that Agm can inhibit the spontaneous discharge, and L-glutamate, Bay K-8644- or L-NAME-induced discharge of neurons in SFO. These inhibitory effects of Agm may be related to the blockade of NMDA receptors and reduction in calcium influx in SFO neurons.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
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pharmacology
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Action Potentials
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drug effects
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Agmatine
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pharmacology
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Animals
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Calcium Channel Agonists
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pharmacology
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Female
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Glutamic Acid
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pharmacology
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Hippocampus
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physiology
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Male
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Neurons
;
physiology
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Rats
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Rats, Sprague-Dawley
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Receptors, Drug
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agonists
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Receptors, N-Methyl-D-Aspartate
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antagonists & inhibitors
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Subfornical Organ
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drug effects
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physiology
10.Inflammation unmasks gabapentin's effect on A delta-fiber evoked excitatory postsynaptic currents in substantia gelatinosa neurons of rat spinal cord.
Zhiliang LIU ; Ruxiang XU ; Kun YANG
Chinese Medical Journal 2003;116(6):883-887
OBJECTIVETo study the analgesic mechanism of gabapentin, an anticonvulsant, during antinociceptive clinical treatment.
METHODSWhole-cell voltage-clamp recordings were taken from adult rat spinal cord slices to investigate the effect of gabapentin on primary afferent A delta-fiber evoked excitatory postsynaptic currents (EPSCs) to substantia gelatinosa (SG) neurons in normal and inflamed (established by plantar injection of carrageenan) rats.
RESULTSGabapentin (5 - 20 micro mol/L for 5 min) depressed dorsal root A delta fiber evoked polysynaptic, but not monosynaptic EPSCs to SG experiencing inflammation by about 25% (n = 10, P < 0.01). However, gabapentin did not depress the evoked polysynaptic or monosynaptic EPSCs in normal rats. Gabapentin failed to block a glutamate receptor subtype, N-methyl-D-aspartate (NMDA), -induced slow excitatory currents on SG neurons.
CONCLUSIONSInflammation, at least in part, unmasks the gabapentin depression on nociception transmission in the dorsal horn, and this depression is not due to the blockade of postsynaptic NMDA receptor.
Acetates ; pharmacology ; Amines ; Animals ; Cyclohexanecarboxylic Acids ; Nerve Fibers, Myelinated ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; physiology ; Sodium Channels ; drug effects ; physiology ; Substantia Gelatinosa ; drug effects ; physiology ; Synaptic Transmission ; drug effects ; Tetrodotoxin ; pharmacology ; gamma-Aminobutyric Acid