• The Korean Journal of Physiology and Pharmacology
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• v.10 no.6
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• pp.303-307
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• 2006

The effects of ethanol on corticostriatal synaptic transmission were examined, using extracellular recording and analysis of population spike amplitudes in rat brain slices, to study how acute ethanol intoxication impairs striatal function. Ethanol caused a decrease in population spike amplitudes in a dose dependent manner ($50{\sim}200mM$). Pretreatment with picrotoxin, a ${\gamma}-amino$ butyric acid $(GABA)_{A}$ receptor antagonist, increased the population spikes but ethanol (100 mM) was still effective in decreasing the population spikes under this condition. In the presence of $_{(DL)}-2-amino-5-phosphonovaleric$ acid (APV), N-methyl-D-aspartate (NMDA) receptor antagonist, the inhibitory action of ethanol on population spikes was not shown. These results suggest that ethanol inhibits the glutamatergic corticostriatal synaptic transmission through blockade of NMDA receptors.

• Journal of Ginseng Research
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• v.24 no.4
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• pp.196-201
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• 2000

Effects of ginsenosides on NaCN-induced neuronal cell death were studied in cultured rat cerebellar granule cells. NaCN produced a concentration-dependent (1-10 mM) reduction of cell viability (measured by frypan blue exclusion test), that was blocked by N-methyl-D-aspartate receptor antagonist (MK-801) and L-type Ca$\^$2+/ channel blocker (verapamil). Pretreatment with ginsenosides (Rb$_1$, Rc, Re, Rf and Rg$_1$) significantly decreased the neuronal cell death in a concentration range of 0.5∼5$\mu\textrm{g}$/ml. Ginsenosides Rb$_1$ and Rc (5 $\mu\textrm{g}$/ml) inhibited glutamate release into medium induced by NaCN (5 mM). NaCN (1 mM)-induced increase of [Ca$\^$2+/], was significantly inhibited by the pretreatment of Rb$_1$ and Rc (5 $\mu\textrm{g}$/ml). Other ginsenosides caused relatively little inhibition on the elevation of glutamate release and of (Ca$\^$2+/). These results suggest that the NaCN-induced neurotoxicity was related to a series of cell responses consisting of glutamate release and [Ca$\^$2+/]i elevation via glutamate (NMDA and kainate) receptors and resultant cell death, and that ginsenosides, especially Rb$_1$ and Rc, prevented the neuronal cell death by the blockade of the NaCN-induced Ca$\^$2+/influx.

• Journal of Chest Surgery
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• v.31 no.5
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• pp.441-450
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• 1998

The medullospinal tract cells are known to play an important role in the control of the cardiovascular activities. To clarify the modes of action of the neurotransmitters on these cells, glutamate, GABA(${\gamma}$-aminobutyric acid) and bicuculline were applicated iontophoretically into the rostral ventrolateral medulla in adult cats anesthetised with ${\alpha}$-chloralose. Followings are the results obtained : 1. The spontaneous activities of the cardiac-related neurons in rostral ventrolateral medulla (RVLM) were increased by the glutamate and decreased by the GABA. 2. Bicuculline, an antagonist of GABA, alone didn't increase the frequency of the action potentials, but could reverse the cellular response to the GABA, simultaneously applicated. 3. GABA seemed to decrease the peak as well as the basal discharge of the neurons in RVLM, but hardly changed their periodicities. 4. The cellular responses of RVLM evoked by the peripheral nerve stimulation could be inhibited by the iontophoretically released GABA. In conclusion, GABA seemed to act as an inhibitory neurotransmitter on the cardiac- related neurons in RVLM of the cats anesthetized with ${\alpha}$-chloralose. But the maintenance of the periodicities of these cells after the application of bicuculline suggested that the afferent activity of the baroreceptor didn't play a key role in the spontaneous activities of the RVLM neurons.

• The Korea Journal of Herbology
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• v.20 no.2
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• pp.115-125
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• 2005

Objectives : Polygalae Radix (PR) from Polygalae tenuifolia (Polygalaceae) has been clinically used as a sedative, anti-inflammatory, and anti-bacterial agent. To extend pharmacological effects of PR in the central nervous system (CNS) on the basis of its CNS protective effect, the present study was conducted to identify the effect of PR, whether it shows the neuroprotective action against excitatory neurotoxicity. Methods : To identify the protective effect of PR to excitatory neuro-toxic agent, the present study was focused on the PR effect on cell death, that was caused by applying NMDA to nerve cell, elevation of $(Ca^{2+})_i$, releasement of glutamate, and ROS generation. Result : 1. PR methanol extract, at the concentration range of 0.05 to 5 g/ml, significantly inhibited NMDA (1 mM)-induced neuronal cell death as well as MK-801 (non competitive NMDA antagonist). 2. PR methanol extract $(0.5\;{\mu}g/ml)$ inhibited NMDA (1 mM)-induced elevation of cytosolic calcium concentration $[Ca^{2+}]_i$. NMDA application in the presence of MK-801 $(10\;{\mu}M)$ failed to produce the increase of $[Ca^{2+}]_i$ through all the measurement time. 3. PR methanol extract $(0.5\;{\mu}g/ml)$ inhibited the NMDA-induced elevation of glutamate release. Also, MK-801 showed similar protective effects. 4. PR methanol extract $(0.5\;{\mu}g/ml)$ inhibited the NMDA-induced elevation of ROS generation. Also, MK-801 showed similar protective effects. Conclusion : The present study provides the availability of PR to exert its protective effect on the neuronal cell death in various neurodegenerative pathophysiological conditions.

• The Korean Journal of Pain
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• v.18 no.1
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• pp.1-9
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• 2005

Background: Spinal metabotropic glutamate receptors (mGluRs) and opioid receptors are involved in the modulation of nociception. Although opioid receptors agonists are active for pain, the effects of the compounds for the mGluRs have not been definitely investigated at the spinal level. We examined the effects of the intrathecal mGluR compounds and morphine in the nociceptive test, and then we further clarified the role of the spinal mGluRs. In addition, the nature of the pharmacological interaction after the coadministration of mGluRs compounds with morphine was determined. Methods: Catheters were inserted into the intrathecal space of male SD rats. For the induction of pain, $50{\mu}l$ of 5% formalin solution or a thermal stimulus was applied to the hindpaw. An isobolographic analysis was used for the evaluation of the drug interaction. Results: Neither group I mGluR compounds nor group III mGluR compounds produced any antinociceptive effect in the formalin test. The group II mGluR agonist (APDC) had little effect on the formalin-induced nociception. The group II mGluR antagonist (LY 341495) caused a dose-dependent suppression of the phase 2 flinching response on the formalin test, but it did not reduce the phase 1 response of the formalin test nor did it increase the withdrawal latency of the thermal stimulus. Isobolographic analysis revealed a synergistic interaction after the intrathecal delivery of a LY 341495-morphine mixture. Conclusions: These results suggest that group II mGluRs are involved in the facilitated processing at the spinal level, and the combination of LY 341495 with morphine may be useful to manage the facilitated pain state.

• Biomedical Science Letters
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• v.11 no.3
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• pp.319-326
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• 2005

It is well known that oxidative stress of reactive oxygen species (ROS) may be a causative factor in the pathenogenesis of bone disorder on osteoblast or osteoclast. The purpose of this study was to evaluate the cytotoxicity of oxidative stress, protective effect of glutamate receptor antagoinst against ROS-induced osteotoxicity, secretion of tumor necrosis factor $(TNF)-\alpha$ and the expression of c-fos gene in the cultured rat osteoblasts and osteoclasts. Cell viability by MTS assay or !NT assay, activity of glutathione peroxidase (GPx), lipid peroxidation (LPO) activity, protein synthesis by sulforhodamine B (SRB) assay, alkaline phosphatase (ALP) activity, lactate dehydrogenase (LDH) activity, MTS assay for NMDA (N-methyl-D-aspartate) receptor antagonist or AMPA/kainate receptor antagonist, measurement for $TNF-\alpha$, and c-fos gene expression were performed after these cells were treated with or without various cocentrations of xanthine oxidase (XO), hypoxanthine (HX), D-2-amino-5-phosphonovaleric acid (APV), 7-chlorokynurenic acid (CKA), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX), respectively. In this study, XO/HX showed decreased cell viability and glutathione peroxidase (GPx) activity, but it showed increased LPO activity, $TNF-\alpha$ secretion and c-fos expression. APV and CKA incresed protein sythesis and ALP activity. While, CNQX or DNQX did not show any protective effect in LDH activity or cell viability. From these results, XO/HX showed cytotoxic effect in cultured rat osteoblast or osteoclast, and also NMDA receptor antagonist such as APV or CKA was effective in blocking XO/HX-induced osteotoxicity in these cultures.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.3
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• pp.187-192
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• 2012

In the present study, the antinociceptive profiles of hop extract were characterized in ICR mice. Hop extract administered orally (from 25 to 100 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Antinociceptive action of hop extract was maintained at least for 60 min. Moreover, cumulative response time of nociceptive behaviors induced with intraplantar formalin injection was reduced by hop extract treatment during the 2nd phases. Furthermore, the cumulative nociceptive response time for intrathecal injection of substance P ($0.7{\mu}g$) or glutamate ($20{\mu}g$) was diminished by hop extract. Intraperitoneal pretreatment with naloxone (an opioid receptor antagonist) attenuated antinociceptive effect induced by hop extract in the writhing test. However, methysergide (a 5-HT serotonergic receptor antagonist) or yohimbine (an ${\alpha}_2$-adrenergic receptor antagonist) did not affect antinociception induced by hop extract in the writhing test. Our results suggest that hop extract shows an antinociceptive property in various pain models. Furthermore, the antinociceptive effect of hop extract may be mediated by opioidergic receptors, but not serotonergic and ${\alpha}_2$-adrenergic receptors.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.6
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• pp.295-301
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• 2003

Striatum plays a crucial role in the movement control and habitual learning. It receives an information from wide area of cerebral cortex as well as an extensive serotonergic (5-hydroxytryptamine, 5-HT) input from raphe nuclei. In the present study, the effects of 5-HT to modulate synaptic transmission were studied in the rat corticostriatal brain slice using in vitro extracellular recording technique. Synaptic responses were evoked by stimulation of cortical glutamatergic inputs on the corpus callosum and recorded in the dorsal striatum. 5-HT reversibly inhibited coticostriatal glutamatergic synaptic transmission in a dose-dependent fashion (5, 10, 50, and $10{\mu}M$), maximally reducing in the corticostriatal population spike (PS) amplitude to $40.1{\pm}5.0$% at a concentration of $50{\mu}M$ 5-HT. PSs mediated by non-NMDA glutamate receptors, which were isolated by bath application of the NMDA receptor antagonist, d,l-2-amino-5-phospohonovaleric acid (AP-V), were decreased by application of $50{\mu}M$ 5-HT. However, PSs mediated by NMDA receptors, that were activated by application of zero $Mg^{2+}$ aCSF, were not significantly affected by $50{\mu}M$ 5-HT. To test whether the corticostriatal synaptic inhibitions by 5-HT might involve a change in the probability of neurotransmitter release from presynaptic nerve terminals, we measured the paired-pulse ratio (PPR) evoked by 2 identical pulses (50 ms interpulse interval), and found that PPR was increased ($33.4{\pm}5.2$%) by 5-HT, reflecting decreased neurotransmitter releasing probability. These results suggest that 5-HT may decrease neurotransmitter release probability of glutamatergic corticostriatal synapse and may be able to selectively decrease non-NMDA glutamate receptor-mediated synaptic transmission.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.279-286
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• 1998

It has been well documented that transient forebrain global ischemia causes selective neuronal degeneration in hippocampal CA1 pyramidal neurons with a delay of a few days. The mechanism of this delayed hippocampal CA1 pyramidal neuronal death (DND) is still controversial. To delineate the mechanisms of the DND, the effects of treatment with MK-801, an NMDA receptor antagonist, kynurenic acid, a NMDA/non-NMDA receptor antagonist, and/or cycloheximide, a protein synthesis inhibitor, on the DND were investigated in male Wistar rats. To examine the participation of apoptotic neuronal death in the DND, TUNEL staining was performed in ischemic brain section. Global ischemia was induced by 4-vessel occlusion for 20 min. All animals in this study showed the DND 3 and 7 days after the ischemic insult. The DND that occured 3 days and 7 days after the ischemia were not affected by pretreatment with MK-801 (1 mg/kg), but markedly attenuated by the pretreatment with kynurenic acid (500 mg/kg). Treatment with cycloheximide (1 mg/kg) also markedly inhibited the DND. The magnitudes of attenuation by the two drugs were similar. The magnitude of attenuation by co-treatments with kynurenic acid and cycloheximide was not greater than that with any single treatment. TUNEL staining was negative in the sections obtained 1 or 2 days after the ischemic insults, but it was positive at hippocampal CA1 pyramidal cells in sections collected 3 days after the ischemia. These results suggested that the DND should be mediated by the activation of non-NMDA receptor, not by the activation of NMDA receptor and that the activation of AMPA receptor should induce the apoptotic process in the DND.

• The Korean Journal of Pain
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• v.12 no.1
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• pp.1-7
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• 1999

Background: To study the role of spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in pain behaviors caused by mild burn, we examined the effect of intrathecal administered ACEA 2085, which has been recently characterized as a high potency competitive AMPA receptor antagonist, on the thermal hyperalgesia state induced by mild burn. Methods: A thermal injury was induced by applying the left hind paw to a thermal surface ($52.5^{\circ}C$) for 45 sec. Thermal escape latency of the hind paw was determined using an underglass thermal stimulus. Thirty min after thermal injury, the paw withdrawal latency (PWL) in injured paw of all groups fell from 10~12 sec to 5~7 sec. At that time, ACEA 2085 (0.01~0.1 mcg) and 6-cyano-7-nitroquinoxalinedione (CNQX, 1~30 mcg) were injected through intrathecal heters in rats with mild burn injury on the right hindpaw. And then, PWL were measured in the both hindpaw every 30 minutes for about three hours. Results: The intrathecal injection of ACEA 2085 produced a dose dependent reversal of the hyperalgesia in the right hindpaw and more potent than CNQX, but had no effect upon the response latency of the normal left hind paw even at the largest doses. All effects were observed at doses that had no significant effect upon motor function. Conclusions: Intrathecal ACEA 2085, highly selective AMPA receptor antagonist produce a dose- dependent reversal of the thermal hyperalgesia evoked mild burn injury. These results suggested that spinal AMPA receptor play an important role in the hyperalgesia induced by mild burn injury.