1.GABAergic inhibition modulates intensity sensitivity of temporally patterned pulse trains in the inferior collicular neurons in big brown bats.
Rui-Hong LUAN ; Fei-Jian WU ; Philip H-S JEN ; Xin-De SUN
Acta Physiologica Sinica 2007;59(6):805-813
The echolocating big brown bats (Eptesicus fuscus) emit trains of frequency-modulated (FM) biosonar signals with duration, amplitude, repetition rate, and sweep structure changing systematically during interception of their prey. In the present study, the sound stimuli of temporally patterned pulse trains at three different pulse repetition rates (PRRs) were used to mimic the sounds received during search, approach, and terminal stages of echolocation. Electrophysiological method was adopted in recordings from the inferior colliculus (IC) of midbrain. By means of iontophoretic application of bicuculline, the effect of GABAergic inhibition on the intensity sensitivity of IC neurons responding to three different PRRs of 10, 30 and 90 pulses per second (pps) was examined. The rate-intensity functions (RIFs) were acquired. The dynamic range (DR) of RIFs was considered as a criterion of intensity sensitivity. Comparing the average DR of RIFs at different PRRs, we found that the intensity sensitivity of some neurons improved, but that of other neurons decayed when repetition rate of stimulus trains increased from 10 to 30 and 90 pps. During application of bicuculline, the number of impulses responding to the different pulse trains increased under all stimulating conditions, while the DR differences of RIFs at different PRRs were abolished. The results indicate that GABAergic inhibition was involved in modulating the intensity sensitivity of IC neurons responding to pulse trains at different PRRs. Before and during bicuculline application, the percentage of changes in responses was maximal in lower stimulus intensity near to the minimum threshold (MT), and decreased gradually with the increment of stimulus intensity. This observation suggests that GABAergic inhibition contributes more effectively to the intensity sensitivity of the IC neurons responding to pulse trains at lower sound level.
Acoustic Stimulation
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Animals
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Bicuculline
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pharmacology
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Chiroptera
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Echolocation
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Electrophysiological Phenomena
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GABA-A Receptor Antagonists
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pharmacology
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Inferior Colliculi
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cytology
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Neurons
;
cytology
2.The role of melatonin receptor and GABAA receptor in the sleeping time prolonged by melatonin in mice.
Fang WANG ; Dan ZOU ; Jing-Cai LI ; Chi HONG ; Li-Bin CHEN ; Xia CHEN
Chinese Journal of Applied Physiology 2003;19(4):402-405
AIMTo observe the role of melatonin receptor and GABAA receptor in sleeping time prolonged by melatonin in mice.
METHODSThe absence of the righting reflex was considered as the sleep onset and the duration of the loss of the righting reflex was recorded as the sleeping time. The effects of receptor agonist and antagonist on hypnotic activity of melatonin were studied in the paper.
RESULTSPrazosin hydrochloride, the blocker of melatonin 3 receptor, didn't affect the sleeping time prolonged by melatonin in mice. GABA, the endogenous agonist of GABA receptor, significantly potentiated the hypnotic activity of melatonin. When picrotoxin, the ligand of picrotoxin site on GABAA receptor, used together with melatonin, it significantly antagonized the sleeping time prolonged by melatonin, however, bicuculline, the specific antagonist of GABA binding site in GABAA receptor, didn't affect the hypnotic activity of melatonin in mice.
CONCLUSIONMelatonin does not exhibit its potentiation sleeping time in mice through melatonin 3 receptor. Hypnotic activity of melatonin may be mediated through picrotoxin site on GABAA receptor.
Animals ; Bicuculline ; pharmacology ; Male ; Melatonin ; physiology ; Mice ; Mice, Inbred Strains ; Picrotoxin ; pharmacology ; Prazosin ; pharmacology ; Receptors, GABA-A ; physiology ; Receptors, Melatonin ; physiology ; Sleep ; physiology
3.Effect of morphine on dorsal horn projection neurons in neuropathic pain rats.
Yan-ping CHEN ; De-quan CAO ; Chao-hua TAN ; Jun-mei XU ; Ye-tian CHANG
Journal of Central South University(Medical Sciences) 2006;31(4):534-537
OBJECTIVE:
To explore the inhibitory effect of spinal topical morphine on the dorsal horn projection neurons in nerve-injured rats and its mechanism.
METHODS:
Single-unit activity of dorsal horn projection neurons was recorded in anesthetized L(5)/L(6) nerve-ligated rats. Allodynia was determined by a behavior test in nerve-injured rats. The evoked neuronal responses to mechanical stimuli applied to the receptive field were determined before and after the spinal topical application of morphine, bicuculline plus morphine, strychnine plus morphine, and both bicuculline and strychnine plus morphine in normal, sham operation, and nerve-injured rats.
RESULTS:
Spinal topical application of 10 micromol/L morphine significantly inhibited the evoked responses of dorsal horn projection neurons in normal, sham, operation and nerve-injured rats. However, the inhibitory effect of morphine was significantly reduced in nerve-injured rats compared with that in normal and sham operation rats. Furthermore, the topical application of 20 micromol/L bicuculline had little effect on the inhibitory effect of morphine in nerve-injured rats but it almost abolished the effect of morphine in normal and sham operation rats. The glycine receptor antagonist strychnine at 4 micromol/L significantly decreased the effect of morphine in nerve-injured, normal, and sham operation rats.
CONCLUSION
The loss of tonic GABAergic inhibition contributes to the reduced inhibitory effect of morphine on dorsal horn projection neurons in nerve-injured rats.
Analgesics, Opioid
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pharmacology
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Animals
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Bicuculline
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pharmacology
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Electrophysiology
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Hyperesthesia
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Male
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Morphine
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pharmacology
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Pain
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etiology
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physiopathology
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Posterior Horn Cells
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physiopathology
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Rats
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Rats, Sprague-Dawley
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Spinal Nerves
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injuries
4.The GABA(A) receptor-mediated inhibitory pathway increases the correlated activities in retinal ganglion cells.
Xue LIU ; Ying-Ying ZHANG ; Hai-Qing GONG ; Pei-Ji LIANG
Acta Physiologica Sinica 2009;61(2):99-107
In the present study, the correlated activities of adjacent ganglion cells of transient subtype in response to full-field white light stimulation were investigated in the chicken retina. Pharmacological studies and cross-correlation analysis demonstrated that application of the GABA(A) receptor antagonist bicuculline (BIC) significantly down-regulated the correlation strength while increasing the firing activities. Meanwhile, application of the GABA(A) receptor agonist muscimol (MUS) potentiated the correlated activities while decreasing the firing rates. However, application of the GABA(C) receptor antagonist (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) did not have a consistent influence on either the firing rates or the correlation strength. These results suggest that in the chicken retina, correlated activities among neighborhood transient ganglion cells can be increased while firing activities are reduced with the activation of GABA(A) receptors. The GABA(A)-receptor-mediated inhibitory pathway may be critical for improving the efficiency of visual information transmission.
Action Potentials
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Animals
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Bicuculline
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pharmacology
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GABA-A Receptor Antagonists
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pharmacology
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Mice
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Muscimol
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pharmacology
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Phosphinic Acids
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pharmacology
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Pyridines
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pharmacology
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Receptors, GABA-A
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metabolism
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Retina
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physiology
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Retinal Ganglion Cells
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physiology
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gamma-Aminobutyric Acid
5.Role of melatonin in spatial learning and memory in rats and its mechanism.
Yin FENG ; Lie-Xiong ZHANG ; Dong-Man CHAO
Acta Physiologica Sinica 2002;54(1):65-70
It has been suggested that melatonin is involved in learning and memory. In the present study, we investigated the effects of melatonin on spatial learning and memory in rats, using Morris water maze and electrophysiological methods. The results are as follows. (1) During a six-day water maze training, the mean escape latency of melatonin group in the last 4 days was 30.02+/-3.6 s, and that of control group was 18.44+/-2.7 s (P<0.01). The crossing annulus coefficient of melatonin group was 25.68+/-2.32%, and that of control group was 43.33+/-2.85% (P<0.01). (2) Microinjection of melatonin into CA1 area inhibited long-term potentiation (LTP). Sixty minutes after tetanus, the field excitory postsynaptic potentials (fEPSP) slope of group C (n=7 0.5 microliter saline) was 169.71+/-6.48 % of the baseline, and that of group M2 (n=6, 2 microgram melatonin) was 114.28+/-1.80% of the baseline. The difference is significant (P<0.01). (3) We also investigated the effects of melatonin on LTP after administration of scopolamine. Sixty minutes after tetanus, the fEPSP slope of group SM (n=6, 2 microgram scopolamine before 2 microgram melatonin) was 113.70+/-5.55% of the baseline. It showed a significant decrease compared with group C (P<0.01). However, there was no difference between groups SM and M2 (P>0.05, i.v.). The results obtained by applying melatonin after bicuculline were different from those after scopolamine. Sixty minutes after tetanus, the fEPSP slope of group BM (n=7, 1 microgram bicuculline before 2 microgram melatonin) was 162.29+/>10.52% of the baseline. Compared with group C, there is no significant difference (P>0.05); but compared with group M2, the difference is significant (P<0.01). Our results showed that application of melatonin in rats significantly inhibited not only spatial learning and memory, but also LTP in CA1 area. Furthermore, the results indicate that the inhibition of LTP by melatonin may not be mediated by cholinergic system, but may be through the modulation of GABAergic system.
Animals
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Bicuculline
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pharmacology
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Female
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Hippocampus
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drug effects
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physiology
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Learning
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drug effects
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Long-Term Potentiation
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drug effects
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Male
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Melatonin
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pharmacology
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Rats
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Rats, Sprague-Dawley
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Scopolamine Hydrobromide
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pharmacology
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Space Perception
;
drug effects
6.Effect of bicuculline on first spike latency of the neurons in the inferior colliculus of mice.
Journal of Southern Medical University 2009;29(5):918-921
OBJECTIVETo evaluate the effect of bicuculline on the first spike latency of the neurons in the inferior colliculus of mice and investigate the role of GABA inhibition in sound signal processing of the neurons.
METHODSIn vivo extracellular recording was performed on the inferior colliculus of 13 BALB/c mice (4 to 5 weeks old) to record the neuronal response to pure tones. Bicuculline, a GABA-A receptor antagonist, was applied to the neurons iontophoretically through one channel in the three-barrel glass-pipettes. The first spike latency and other response properties of the characteristic frequency were recorded for analysis.
RESULTSA total of 30 well-isolated single neurons were recorded. Increased spike counts characterized 96% of the neurons, with either increased (40%) or decreased (60%) latency of neuronal responses. Characteristic frequency alterations occurred in 50% of the neurons with increased spike latency, and the minimum threshold showed linear changes.
CONCLUSIONGABAergic inhibition may participate in the latency formation and increased frequency selectivity of mouse inferior colliculus neurons by lateral inhibition. The changes in the first spike latency can be indicative of the information integration in GABAergic neurons at the synaptic level.
Acoustic Stimulation ; psychology ; Action Potentials ; drug effects ; Animals ; Bicuculline ; pharmacology ; Female ; GABA Antagonists ; pharmacology ; Inferior Colliculi ; physiology ; Male ; Mice ; Mice, Inbred BALB C ; Neurons ; physiology ; gamma-Aminobutyric Acid ; physiology
7.The influence of GABAA receptor on the analgesic action of intrathecally injected oxysophoridine.
Guang YANG ; Jin-xian GAO ; Zheng-hong YI ; Lin YAN ; Yuan-Xu JIANG
Acta Pharmaceutica Sinica 2011;46(5):534-538
.This study is to investigate the analgesic effect produced by intrathecal injection (ith) of oxysophoridine (OSR) and the mechanism of GABAA receptor. Warm water tail-flick test was used to detect the analgesic effect of OSR (12.5, 6.25, and 3.13 mg.kg-1 ith) and to observe the influence of GABA (gamma aminobutyric acid) agonist or antagonist on the analgesic effect of OSR in mice. Immunohistochemistry method were used to detect the influence of OSR (12.5 mg.kg-1, ith) on the GABAARalpha1 protein expression in spinal cord. The results obtained covers that OSR (12.5 and 6.25 mg.kg-, ith) alleviates pain significantly with the warm water tail-flick test (P<0.05, P<0.01), the rate of pain threshold increases by 68.45%; GABA and muscimol (MUS) produces analgesic synergism together with the OSR, picrotoxin (PTX) and bicuculline (BIC) antagonize the analgesic effect of OSR; OSR (12.5 mg.kg-1, ith) significantly increase the positive number of GABAARalpha1 nerve cell in spinal cord (P<0.01) and significantly decrease the average grey levels (P<0.01). In conclusion, OSR intrathecal injection has significant analgesic effect. And GABAA receptor in spinal cord is involved in the analgesic mechanism.
Alkaloids
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administration & dosage
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pharmacology
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Analgesics
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administration & dosage
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pharmacology
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Animals
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Bicuculline
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pharmacology
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Female
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GABA-A Receptor Agonists
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pharmacology
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GABA-A Receptor Antagonists
;
pharmacology
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Injections, Spinal
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Male
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Mice
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Muscimol
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pharmacology
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Pain Threshold
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drug effects
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Picrotoxin
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pharmacology
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Random Allocation
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Receptors, GABA-A
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metabolism
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Spinal Cord
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metabolism
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gamma-Aminobutyric Acid
;
pharmacology
8.Effects of GABA on pancreatic exocrine secretion of rats.
Hyung Seo PARK ; Hyoung Jin PARK
Journal of Korean Medical Science 2000;15(Suppl):S24-S26
Since GABA and its related enzymes had been determined in beta-cells of pancreas islets, effects of GABA on pancreatic exocrine secretion were investigated in the isolated perfused rat pancreas. GABA, given intra-arterially at concentrations of 3, 10, 30 and 100 microM, did not exert any influence on spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However, GABA further elevated cholecystokinin (10 pM)-, gastrin-releasing peptide (100 pM)- or electrical field stimulation-induced pancreatic secretions of fluid and amylase, dose-dependently. The GABA-enhanced CCK-induced pancreatic secretions were completely blocked by bicuculline (10 microM), a GABAA receptor antagonist but not affected by saclofen (10 microM), a GABA(B) receptor antagonist. The enhancing effects of GABA (30 microM) on CCK-induced pancreatic secretions were not changed by tetrodotoxin (1 microM) but partially reduced by cyclo-(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 microM), a somatostatin antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by secretagogues, which stimulate enzyme secretion predominantly, via GABA(A) receptors in the rat pancreas. The enhancing effect of GABA is partially mediated by inhibition of islet somatostatin release. GABA does not modify the activity of intrapancreatic neurons.
Amylases/metabolism
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Animal
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Baclofen/pharmacology
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Baclofen/analogs & derivatives*
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Bicuculline/pharmacology
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Cholecystokinin/metabolism
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Dose-Response Relationship, Drug
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Electric Stimulation
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GABA/pharmacology*
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GABA Antagonists/pharmacology
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Gastrin-Releasing Peptide/metabolism
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Hormones/pharmacology
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In Vitro
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Pancreas/secretion*
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Pancreas/enzymology
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Pancreas/drug effects*
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Rats
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Receptors, GABA-A/metabolism
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Secretin/metabolism
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Somatostatin/pharmacology
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Tetrodotoxin/pharmacology
9.Kir2.1 Channel Regulation of Glycinergic Transmission Selectively Contributes to Dynamic Mechanical Allodynia in a Mouse Model of Spared Nerve Injury.
Yiqian SHI ; Yangyang CHEN ; Yun WANG
Neuroscience Bulletin 2019;35(2):301-314
Neuropathic pain is a chronic debilitating symptom characterized by spontaneous pain and mechanical allodynia. It occurs in distinct forms, including brush-evoked dynamic and filament-evoked punctate mechanical allodynia. Potassium channel 2.1 (Kir2.1), which exhibits strong inward rectification, is and regulates the activity of lamina I projection neurons. However, the relationship between Kir2.1 channels and mechanical allodynia is still unclear. In this study, we first found that pretreatment with ML133, a selective Kir2.1 inhibitor, by intrathecal administration, preferentially inhibited dynamic, but not punctate, allodynia in mice with spared nerve injury (SNI). Intrathecal injection of low doses of strychnine, a glycine receptor inhibitor, selectively induced dynamic, but not punctate allodynia, not only in naïve but also in ML133-pretreated mice. In contrast, bicuculline, a GABA receptor antagonist, induced only punctate, but not dynamic, allodynia. These results indicated the involvement of glycinergic transmission in the development of dynamic allodynia. We further found that SNI significantly suppressed the frequency, but not the amplitude, of the glycinergic spontaneous inhibitory postsynaptic currents (gly-sIPSCs) in neurons on the lamina II-III border of the spinal dorsal horn, and pretreatment with ML133 prevented the SNI-induced gly-sIPSC reduction. Furthermore, 5 days after SNI, ML133, either by intrathecal administration or acute bath perfusion, and strychnine sensitively reversed the SNI-induced dynamic, but not punctate, allodynia and the gly-sIPSC reduction in lamina IIi neurons, respectively. In conclusion, our results suggest that blockade of Kir2.1 channels in the spinal dorsal horn selectively inhibits dynamic, but not punctate, mechanical allodynia by enhancing glycinergic inhibitory transmission.
Animals
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Bicuculline
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pharmacology
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Disease Models, Animal
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Glycine
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metabolism
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Hyperalgesia
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drug therapy
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etiology
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metabolism
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Imidazoles
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pharmacology
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Inhibitory Postsynaptic Potentials
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drug effects
;
physiology
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Male
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Mice, Inbred C57BL
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Neurons
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drug effects
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metabolism
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Neurotransmitter Agents
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pharmacology
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Peripheral Nerve Injuries
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drug therapy
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metabolism
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Phenanthrolines
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pharmacology
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Potassium Channels, Inwardly Rectifying
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antagonists & inhibitors
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metabolism
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Receptors, GABA-A
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metabolism
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Receptors, Glycine
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metabolism
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Strychnine
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pharmacology
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Synaptic Transmission
;
drug effects
;
physiology
;
Tissue Culture Techniques
;
Touch
10.GABA mediaties the inhibitory effect of lateral amygdaloid nucleus stimulation on the acoustic response of neurons in A I cortex: An in vivo microiontophoretic study.
De-Fu HE ; Fu-Jun CHEN ; Shao-Ci ZHOU
Acta Physiologica Sinica 2004;56(3):374-378
Experiments were performed on Sprague Dawley rats with multibarrel microelectrode technique. The effects of acoustic response of A I cortex neurons produced by electrical stimulation of lateral amygdaloid nucleus (LA) and the influence of GABA were observed. Experimental results showed that iontophoretic administration of GABA caused a pronounced inhibition of the electrical activity of A-I neurons. Blockade of GABA(A) with bicuculline (BIC) facilitated the acoustic response. The acoustic response of A-I neurons was inhibited when the LA was stimulated. Iontophoretic application of GABA resulted in a similar inhibitory effect as that of LA stimulation. Blockade of GABA(A) with bicuculline reversed the inhibitory effect of LA stimulation on the acoustic response of A-I neurons. In contrast, application of strychnine, a glycine receptor antagonist, could not reverse the inhibitory effect of LA. Baclofen, a GABA(B) agonist, did not affect the acoustic response of the auditory neurons. These results indicate that GABA is the ultimate transmitter which mediates the LA stimulation-induced inhibition of the acoustic response of A-I neurons in rats, possibly via the GABA(A) receptor.
Acoustic Stimulation
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Amygdala
;
physiology
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Animals
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Baclofen
;
pharmacology
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Bicuculline
;
pharmacology
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Cerebral Cortex
;
physiology
;
Electric Stimulation
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Evoked Potentials, Auditory
;
physiology
;
GABA Agonists
;
pharmacology
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GABA Antagonists
;
pharmacology
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Iontophoresis
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methods
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Male
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Microelectrodes
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Neurons
;
physiology
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Rats
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Rats, Sprague-Dawley
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Receptors, GABA-A
;
physiology
;
gamma-Aminobutyric Acid
;
physiology