No abstract available.
6-Cyano-7-nitroquinoxaline-2,3-dione* ; Cycloheximide* ; Dizocilpine Maleate*

PURPOSE: The goal of this study was to investigate the effects of bicuculline(BIC) on the excitability of visual cortex, observe the induction of epileptiform activity and define the characteristics of spontaneous activity. METHODS: We divided 19 to 23-day-old Sprague-Dawley rats into 3 groups by the concentration of BIC:5(n=10), 20(n=12), and 40(n=10) microM. The slices from the rats were incubated in artificial CSF for 1 hour, and then extracellular recordings were performed. RESULTS: Spontaneous epileptiform activities were observed in all of the BIC groups. The latencies of 5, 20, and 40 microM BIC were 31.6+/-13.0, 34.0+/-11.9, and 6.3+/-3.2 min. The frequencies of 5, 20, and 40 microM BIC were 1.1+/-0.5, 2.7+/-1.8, and 19.1+/-23.3 min-1. The amplitudes of 5, 20, and 40 microM BIC were 5.4+/-1.4, 6.9+/-0.9, 11.1+/-1.3 mV. The durations of 5, 20, and 40 microM BIC were 444.6+/-169.1, 865.2+/-151.2, and 1,014.7+/-613.8 ms. CONCLUSION: BIC is associated with increased excitability in the visual cortex and induces spontaneous epileptiform activities. This induction was decreased by D-AP5 or CNQX.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Animals ; Bicuculline* ; Rats ; Rats, Sprague-Dawley ; Visual Cortex

PURPOSE: The goal of the present study was to investigate the effect of low magnesium on the excitability of visual cortex, observe the induction of epileptiform activity, and define the characteristics of spontaneous activity. METHODS: We divided 19-23 days-old Sprague-Dawley rats into three groups; they were divided by the concentration of Mg, 1 (n=10), 0.5 (n=13), and 0 (n=14) mM. The visual cortex slices from brain were incubated in artificial CSF for one hour, and then extracellular recordings were performed. RESULTS: The latency of interictal epileptiform activity in 0.5 and 0 mM Mg was 26.9+/-11.7 and 13.3+/-2.7 min, the frequency was 1.1+/-0.7 and 5.7+/-0.7 min-1, the amplitude was 1.0+/-0.3 and 1.4+/-0.4 mV, the duration was 15.1+/-15.4 and 587.4+/-398.0 ms. The latency of ictal epileptiform activity in 0 mM Mg was 15.5+/-8.0 min, the frequency was 53.8+/-16.3 /event, the amplitude was 2.9+/-0.7 mV, the duration was 25.2+/-6.0 s. CONCLUSIONS: Low Mg showed the increased excitability in the visual cortex and induced the interictal and ictal spontaneous epileptiform activity. This induction was abolished by D-AP5 and decreased by CNQX. This result may provide insights into the events underlying the epileptogenesis.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Animals ; Brain ; Magnesium* ; Rats* ; Rats, Sprague-Dawley ; Visual Cortex*

PURPOSE: The goal of the present study was to investigate the effects of 4-aminopyridine(4-AP) on the excitability of visual cortex, observe the induction of epileptiform activity and define the characteristics of spontaneous activity. METHODS: We divided 19 to 23-day-old Sprague-Dawley rats into 3 groups by the concentration of 4-AP:5(n=10), 50(n=11), and 100(n=12) microM. The slices from their brains were incubated in artificial CSF for 1 hour, and then extracellular recordings were performed. RESULTS: Spontaneous epileptiform activities were observed in 50 and 100 microM 4-AP groups. The latencies of interictal epileptiform activity were 7.8+/-1.1 and 5.8+/-0.9 min, the frequencies 1.8+/-0.2 and 24.1+/-6.6 min-1, the amplitudes 0.7+/-0.1 and 2.8+/-0.5 mV, and the durations 238.0+/-57.8 and 242.2+/-70.0 ms in 50 and 100 microM 4-AP groups respectively. The latencies of ictal epileptiform activity were 21.0+/-9.8 and 6.7+/-2.3 min, the frequencies 116.2+/-46.7 and 193.7+/-26.4/event, the amplitudes 3.1+/-0.8 and 2.8+/-0.9 mV, and the durations 26.9+/-27.6, 35.2+/-12.6 s in 50 and 100 microM 4-AP groups respectively. CONCLUSION: 4-AP showed increased excitability in the visual cortex and induced interictal and ictal spontaneous epileptiform activity. This induction was decreased by D- AP5 or CNQX. Those results suggest that both types of inotropic excitatory amino acid receptors are overactivated and contribute to seizure initiation and propagation.
4-Aminopyridine* ; 6-Cyano-7-nitroquinoxaline-2,3-dione ; Brain ; Rats, Sprague-Dawley ; Receptors, Glutamate ; Seizures ; Visual Cortex

Toxic effect of oxygen radicals and cardioprotective effect of N -methyl -D -aspartate (NMDA) receptor antagonists against xanthine oxidase (XO) and hypoxanthine (HX)-induced cardiotoxicity were measured in order to elucidate the mechanism of cardiotoxicity on cultured mouse myocardial cells. MTT assay was performed after myocardial cells were cultured for 12 hours at various concentrations of XO/HX alone or with D -2 -amino -5 -phosphonovaleric acid (APV) or 6 - cyano -7 -nitroquinoxaline -2,3 -dione (CNQX). In this study, XO/HX was toxic in a time -and dose -dependent manners on cultured myocardial cells, and midcytotoxicity value 50 (MTT50) was at 30 mU/ml XO and 0.1 mM HX after myocardial cells were grown for 12 hours in media containing 1 ~50 mU/ml XO and 0.1 mM HX. When cultures were treated with 30 mU/ml XO and 0.1 mM HX flus 20 80 microM APV for 12 hours, cell viability was increased remarkably, while treatment with 30 mU/ml XO and 0.1 mM HX flus 10 ~50 microM CNQX did not show any protective effect against XO/HX -induced neurotoxicity. From the above results, it is suggested that oxygen radicals are toxic on cultured mouse myocardial cells by the decrease of cell viability, and NMDA receptor antagonists such as APV are very effective in the prevention of myocardial toxicity induced by oxygen radicals.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Animals ; Cell Survival ; Hypoxanthine ; Mice ; N-Methylaspartate* ; Oxygen* ; Reactive Oxygen Species* ; Xanthine Oxidase

PURPOSE: The goal of this study was to investigate the effect of tetraethylammonium (TEA) on the excitability of visual cortex, and observe the induction of epileptiform activity. Also, it was aimed to define the characteristics of spontaneous activity and observe the effect of GABAA antagonist, NMDA antagonist and non-NMDA antagonist on the TEA-induced epileptiform activity. METHODS: The visual cortex slices in this study were obtained from 19 to 23 day-old Sprague-Dawley rats. Extracellular cellular recording was performed to observe the induction of epileptiform discharge perfused by artificial CSF containing 1, 5 and 10 mM TEA and the effect of 10 ?M 6-cyano-7-nitroquinoxaline-dione disodium(CNQX) and 50 microM D-(-)-2-amino-5-phosphonopentanoic acid(D-AP5) on the 10 mM TEA-induced epileptiform activity. RESULTS: Spontaneous epileptiform activities were observed in 5 and 10 mM TEA groups. The addition of 5 ?M BIC blocked the TEA-induced spontaneous ictal epileptiform activity but didn't block the TEA-induced spontaneous interictal epileptiform activity. The addition of 10 ?M CNQX shortened duration, decreased frequency and amplitude of the TEA-induced spontaneous epileptiform activity. The addition of 50 microM D-AP5 blocked the TEA-induced spontaneous ictal and interictal epileptiform activity. CONCLUSION: TEA induced the increased excitability in the visual cortex and spontaneous epileptiform activity. 5 ?M BIC blocked the TEA-induced spontaneous ictal epileptiform activity and GABAA antagonist BIC plays a role in limiting the epileptiform discharge. The TEA-induced spontaneous epileptiform activity induction was decreased by CNQX and blocked by D-AP5. NMDA and non-NMDA are required to modify the TEA-induced spontaneous epileptiform activity.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Animals ; GABA Antagonists ; N-Methylaspartate ; Rats* ; Rats, Sprague-Dawley ; Tea ; Tetraethylammonium ; Visual Cortex*

BACKGROUND: The purpose of this study was to investigate the effect of potassium, bicuculline (BIC) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on epileptiform activity induced by pilocarpine in the rat visual cortex slices. METHODS: In the rat visual cortex slices, we observed the change of pilocarpine-induced epileptiform discharges using extracellular recordings during perfusion of artificial cerebro-spinal fluid (ACSF) with various potassium concentrations ([K+], 2.5, 5, 7.5 and 10 mM) and ACSF with 10 micrometer BIC and 20 micrometer CNQX under 7.5 mM [K+]. RESULTS: Spontaneous interictal epileptiform activity induced by pilocarpine was observed in 5 mM or higher [K+] and ictal discharge was only detected in 7.5 mM [K+]. Increase of [K+] from 2.5 to 7.5 mM not only resulted in the increase of frequency and amplitude of epileptiform activity but also favored the transformation of pilocarpine-induced interictal activity into ictal activity in the rat visual cortex. However, in 10 mM [K+], the ictal discharge was unprovoked and interictal activity was provoked with decreased frequency and amplitude. The spontaneous ictal discharge was blocked but interictal activity was maintained with increased frequency and amplitude by BIC. Interictal and ictal activities were completely blocked by CNQX. CONCLUSIONS: These results suggested that the extracellular potassium concentration, GABA system, and non-NMDA mechanism seemed to be involved in the development and maintenance of pilocarpine-induced epileptiform activity in the rat visual cortex.
6-Cyano-7-nitroquinoxaline-2,3-dione* ; Animals ; Bicuculline* ; gamma-Aminobutyric Acid ; Perfusion ; Pilocarpine* ; Potassium* ; Rats* ; Visual Cortex*

Whole bee venom (WBV) and its major component, melittin, have been reported to induce long-lasting spontaneous flinchings and hyperalgesia. The current study was designed to elucidate the peripheral and spinal mechanisms of N-methyl-D-aspartate (NMDA) and non-NMDA receptors by which intraplantar (i.pl.) injection of WBV and melittin induced nociceptive responses. Changes in mechanical threshold and flinching behaviors were measured after the injection of WBV (0.04 mg or 0.1 mg/paw) and melittin (0.02 mg or 0.05 mg/paw) into the mid-plantar area of a rat hindpaw. MK-801 and CNQX (6-cyano-7-nitroquinoxaline-2, 3-dione disodium) were administered intrathecally (i.t. 10microgram) or i.pl. (15microgram) 15 min before or i.t. 60 min after i.pl. WBV and melittin injection. Intrathecal pre- and post- administration of MK-801 and CNQX significantly attenuated the ability of high dose WBV and melittin to reduce paw withdrawal threshold (PWT). In the rat injected with low dose, but not high dose, of WBV and melittin, i.pl. injection of MK-801 effectively suppressed the decrease of PWTs only at the later time-points, but the inhibitory effect of CNQX (i.pl.) was significant at all time-point after the injection of low dose melittin. High dose WBV- and melittin-induced spontaneous flinchings were significantly suppressed by i.t. administration of MK-801 and CNQX, and low dose WBV- and melittin-induced flinchings were significantly reduced only by intraplantarly administered CNQX, but not by MK-801. These experimental flinchings suggest that spinal, and partial peripheral mechanisms of NMDA and non-NMDA receptors are involved in the development and maintenance of WBV- and melittin-induced nociceptive responses.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Animals ; Bee Venoms* ; Bees* ; Dizocilpine Maleate ; Hyperalgesia ; Melitten* ; N-Methylaspartate* ; Rats*

PURPOSE: The goal of this study was to investigate the effect of increase of K on the excitability of the visual cortex under GABA antagonist, carbamazepine(CBZP), 6-cyano-7-nitroquinoxaline-dione disodium(CNQX) and D-(-)-2-amino-5-phosphonopentanoic acid(D-AP5) on the increase of K-induced epileptiform activity. METHODS: The visual cortex slices were obtained from Sprague-Dawley rats. Extracellular recordings were performed to observe the induction of epileptiform discharges perfused by artificial CSF(ACSF) with an increase of K and the effect of 0.5 and 1 mM CBZP, 10 micrometer CNQX and 50 micrometer D-AP5 on the increase of K-induced epileptiform activity. RESULTS: Spontaneous epileptiform activities were increased by ACSF with 10 mM K under bicuculline compared to 4 mM K. CBZP blocked and 10 micrometer CNQX and 50 micrometer D-AP5 decreased the 10 mM K-induced spontaneous epileptiform activity. CONCLUSION: An increase of K augmented spontaneous epileptiform activity. This experimental model increased the excitability of the brain, which may be influenced by GABA. CBZP blocked the increase of K-induced epileptiform activity, which showed the increase of excitability. An increase of K-induced epileptiform activity was decreased by CNQX and D-AP5, which may show the attenuation of voltage-dependent low magnesium effect and decrease the excitability in terms of synapse induction.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Animals ; Bicuculline ; Brain ; Carbamazepine* ; GABA Antagonists* ; gamma-Aminobutyric Acid* ; Magnesium ; Models, Theoretical ; Rats* ; Rats, Sprague-Dawley ; Synapses ; Visual Cortex*

GABA (-aminobutyric acid) is one of the important neurotransmitters in the central nervous system of mammals and its action is variable according to the maturation phases of neurons. The neurons of early cultural days (less than 7 days) have been used for a developing neuronal model, while the neurons of later days (over 3 weeks) used for a mature model. This study was performed to investigate the electrophysiological property of GABAergic synapses in the hippocampal neurons cultured for 10 to 14 days which are considered to be transitional period between the developing and the mature phases. Membrane potential was depolarized and a inward transmembrane current was induced by 20 M GABA infusion. Frequency and amplitude of spontaneous postsynaptic currents (PSCs) were inhibited during the GABA infusion, but decay time constant was not affected significantly. In most hippocampal neurons, no GABAergic PSCs were observed during the administration of 0.5 M TTX, 50 M APV and 10 M CNQX. In the neurons counting 25% approximately, however, small persisted PSCs showed the existence of GABAergic synapses which were blocked by 10 M bicuculine. As the functional property of isolated GABAergic synapses, amplitude of GABAergic PSCs were diminished, and decay time constants and rising times were prolonged during the 20 M GABA infusion in all recorded neurons. In conclusion, approximately 25% of the hippocmpal neurons cultured 10 to 14 days used GABA as well as glutamate as a neurotransmitter. It seems that the GABAergic synapses composed of functionally homogenous GABAA receptors act as inhibitory modulator of the excitatory signal transmission.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Animals ; Central Nervous System ; gamma-Aminobutyric Acid* ; Glutamic Acid ; Mammals ; Membrane Potentials ; Neurons* ; Neurotransmitter Agents ; Rats* ; Synapses ; Synaptic Potentials