fg-9041 and Epilepsy

Following a traumatic brain injury (TBI), 5-50% of patients will develop posttraumatic epilepsy (PTE) with children being particularly susceptible. Currently, PTE cannot be prevented and there is limited understanding of the underlying epileptogenic mechanisms. We hypothesize that early after TBI the brain undergoes distinct cellular and synaptic reorganization that facilitates cortical excitability and promotes the development of epilepsy.. To examine the effect of pediatric TBI on cortical excitability, we performed controlled cortical impact (CCI) on juvenile rats (postnatal day 17). Following CCI, animals were monitored for the presence of epileptiform activity by continuous in vivo electroencephalography (EEG) and/or sacrificed for in vitro whole-cell patch-clamp recordings.. Following a short latent period, all animals subjected to CCI developed spontaneous recurrent epileptiform activity within 14 days. Whole-cell patch-clamp recordings of layer V pyramidal neurons showed no changes in intrinsic excitability or spontaneous excitatory postsynaptic currents (sEPSCs) properties. However, the decay of spontaneous inhibitory postsynaptic currents (sIPSCs) was significantly increased. In addition, CCI induced over a 300% increase in excitatory and inhibitory synaptic bursting. Synaptic bursting was prevented by blockade of Na(+)-dependent action potentials or select antagonism of glutamate or GABA-A receptors, respectively.. Our results demonstrate that CCI in juvenile rats rapidly induces epileptiform activity and enhanced cortical synaptic bursting. Detection of epileptiform activity early after injury suggests it may be an important pathophysiological component and potential indicator of developing PTE.

Topics: Animals; Animals, Newborn; Biophysics; Brain Injuries; Cerebral Cortex; Disease Models, Animal; Electric Stimulation; Electroencephalography; Epilepsy; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; In Vitro Techniques; Neurons; Patch-Clamp Techniques; Quinoxalines; Rats; Rats, Sprague-Dawley; Valine

In vitro studies performed on brain slices demonstrate that the potassium channel blocker 4-aminopyridine (4AP, 50 microM) discloses electrographic seizure activity and interictal discharges. These epileptiform patterns have been further analyzed here in a isolated whole guinea pig brain in vitro by using field potential recordings in olfactory and limbic structures. In 8 of 13 experiments runs of fast oscillatory activity (fast runs, FRs) in the piriform cortex (PC) propagated to the lateral entorhinal cortex (EC), hippocampus and occasionally to the medial EC. Early and late FRs were asynchronous in the hemispheres showed different duration [1.78 +/- 0.51 and 27.95 +/- 4.55 (SD) s, respectively], frequency of occurrence (1.82 +/- 0.49 and 34.16 +/- 6.03 s) and frequency content (20-40 vs. 40-60 Hz). Preictal spikes independent from the FRs appeared in the hippocampus/EC and developed into ictal-like discharges that did not propagate to the PC. Ictal-like activity consisted of fast activity with onset either in the hippocampus (n = 6) or in the mEC (n = 2), followed by irregular spiking and sequences of diffusely synchronous bursts. Perfusion of the N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid (100 microM) did not prevent FRs, increased the duration of limbic ictal-like discharges and favored their propagation to olfactory structures. The AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (50 microM) blocked ictal-like events and reduced FRs. In conclusion, 4AP-induced epileptiform activities are asynchronous and independent in olfactory and hippocampal-entorhinal regions. Epileptiform discharges in the isolated guinea pig brain show different pharmacological properties compared with rodent in vitro slices.

Topics: 2-Amino-5-phosphonovalerate; 4-Aminopyridine; Animals; Brain; Cerebral Cortex; Entorhinal Cortex; Epilepsy; Excitatory Amino Acid Antagonists; Guinea Pigs; Hippocampus; In Vitro Techniques; Limbic System; Periodicity; Quinoxalines; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Seizures; Time Factors

It has been reported that the inhibitory postsynaptic potential (IPSP) is abolished before the excitatory postsynaptic potential (EPSP) when the extracellular concentration of Ca(2+) ([Ca(2+)](o)) is removed gradually in hippocampal slices. However, the low-Ca(2+) nonsynaptic epileptiform activity does not appear until the [Ca(2+)](o) is decreased to a level sufficient to depress the excitatory synaptic transmission. This suggests the hypothesis that the suppression of excitatory synaptic transmission itself could facilitate the generation of epileptiform activity. In the present study, we tested this hypothesis and developed a new model of nonsynaptic epileptiform activity by gradually raising the neuronal excitability and blocking the synaptic transmission with high K(+), zero Ca(2+) and calcium chelator ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) in the CA1 region of hippocampus in vivo. The changes of synaptic transmission and recurrent inhibitory activity during this process were evaluated by measuring the amplitude of the population spikes (PS) in response to paired-pulse orthodromic stimulation. The results show that the epileptiform activity appeared only when the excitatory synaptic transmission was depressed by further lowering [Ca(2+)](o) with EGTA. Similar epileptiform activity could be induced when EGTA was replaced by the excitatory postsynaptic amino acid antagonists D-(-)-2-amino-5-phosphonopentanoic acid (APV) plus 6,7-dinitroquinoxaline-2,3-dione (DNQX) or APV alone but not DNQX alone. The combination application of APV and cadmium enhanced the epileptiform activity. These results suggest that the suppression of excitatory synaptic transmission can facilitate the appearance of epileptiform activity in solution with high K(+) and low Ca(2+) in vivo. These data provide new information to be considered in the development of antiepileptic drugs. They also suggest a possible mechanism to explain the fact that low-frequency electrical stimulation can suppress epileptiform activity.

Topics: 2-Amino-5-phosphonovalerate; Animals; Cadmium; Calcium; Chelating Agents; Egtazic Acid; Epilepsy; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Female; Hippocampus; Male; Organ Culture Techniques; Potassium; Quinoxalines; Rats; Rats, Sprague-Dawley; Synaptic Transmission

The involvement of glutamatergic and GABAergic mechanisms in the behavioral effects induced by the intrastriatal injection of 5-aminolevulinic acid (ALA) (1-8 mgr;mol/2 mgr;l), a metabolite that accumulates in porphyrias, was evaluated. ALA administration to adult female rats increased locomotor activity, induced clonic convulsions and elicited dose-dependent body asymmetry assessed by the elevated body swing test. ALA-induced convulsions were prevented by intrastriatal preadministration of the glutamate antagonists, 6, 7-dinitroquinoxaline-2,3-dione (8 nmol/0.5 microl) or dizocilpine (2. 5 nmol/0.5 microl), but not by the GABA agonist, muscimol (46 pmol/0. 5 microl). Body asymmetry was prevented only by 6, 7-dinitroquinoxaline-2,3-dione pretreatment. A higher dose of muscimol (92 pmol/0.5 microl) prevented both ALA-induced convulsions and body asymmetry. However, this dose of muscimol induced motor biases, which make difficult to ascertain the involvement of GABA(A) receptors in ALA-induced behavioral effects. This study suggests that glutamatergic mechanisms underlie the ALA-induced convulsions and body asymmetry. The present results may be of value in understanding the physiopathology of the neurological dysfunction occurring in acute porphyrias.

Topics: Aminolevulinic Acid; Animals; Convulsants; Corpus Striatum; Dizocilpine Maleate; Epilepsy; Excitatory Amino Acid Antagonists; Female; GABA Agonists; gamma-Aminobutyric Acid; Glutamic Acid; Microinjections; Muscimol; Quinoxalines; Rats; Rats, Wistar

Activation of cholinergic mechanisms in the pontine reticular formation by local microinjections of carbachol was shown to induce pontine electrographic seizures and clonic convulsions. In this study we found that glutamate microinjections into the pons induced similar electrographic seizures and clonic convulsions. Microinjections into the PRF of glutamate in subconvulsive doses prior to carbachol potentiated the epileptogenic effect of carbachol. The duration of the seizure activity increased and the convulsions became more severe. The NMDA receptor antagonist MK-801 and the non-NMDA receptor antagonists DNQX significantly reduced the potentiating effect of glutamate. These results indicate a possible role of EAA receptors in the generation of epilepsy in the pons. They also suggest the importance of studying the role of synergistic interactions between EAA mechanisms and cholinergic mechanisms in the various pontine functions.

Topics: Animals; Brain Stem; Carbachol; Cholinergic Agonists; Dizocilpine Maleate; Drug Synergism; Epilepsy; Excitatory Amino Acid Antagonists; Excitatory Amino Acids; Glutamic Acid; Male; Microinjections; Pons; Quinoxalines; Rats; Receptors, N-Methyl-D-Aspartate; Time Factors

Under conditions of low [Ca(2+)](o) and high [K(+)](o), the rat dentate granule cell layer in vitro develops recurrent spontaneous prolonged field bursts that resemble an in vivo phenomenon called maximal dentate activation. To understand how pH changes in vivo might affect this phenomenon, the slices were exposed to different extracellular pH environments in vitro. The field bursts were highly sensitive to extracellular pH over the range 7.0-7.6 and were suppressed at low pH and enhanced at high pH. Granule cell resting membrane potential, action potentials, and postsynaptic potentials were not significantly altered by pH changes within the range that suppressed the bursts. The pH sensitivity of the bursts was not altered by pharmacologic blockade of N-methyl-D-aspartate (NMDA), non-NMDA, and GABA(A) receptors at concentrations of these agents sufficient to eliminate both spontaneous and evoked synaptic potentials. Gap junction patency is known to be sensitive to pH, and agents that block gap junctions, including octanol, oleamide, and carbenoxolone, blocked the prolonged field bursts in a manner similar to low pH. Perfusion with gap junction blockers or acidic pH suppressed field bursts but did not block spontaneous firing of single and multiple units, including burst firing. These data suggest that the pH sensitivity of seizures and epileptiform phenomena in vivo may be mediated in large part through mechanisms other than suppression of NMDA-mediated or other excitatory synaptic transmission. Alterations in electrotonic coupling via gap junctions, affecting field synchronization, may be one such process.

Topics: Animals; Calcium; Dentate Gyrus; Electrophysiology; Epilepsy; Excitatory Amino Acid Antagonists; Gap Junctions; Hydrogen-Ion Concentration; Hypnotics and Sedatives; In Vitro Techniques; Male; Octanols; Oleic Acids; Periodicity; Potassium; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, GABA-A; Receptors, N-Methyl-D-Aspartate; Seizures; Synapses; Synaptic Transmission

Limbic epilepsy is a chronic condition associated with a broad zone of seizure onset and pathology. Studies have focused mainly on the hippocampus, but there are indications that changes occur in other regions of the limbic system. This study used in vitro intracellular recording and histology to examine alterations to the physiology and anatomy of the basal nucleus of the amygdala in a rat model of chronic limbic epilepsy characterized by spontaneously recurring seizures. Epileptic pyramidal neuron responses evoked by stria terminalis stimulation revealed hyperexcitability characterized by multiple action potential bursts and no evident inhibitory potentials. In contrast, no hyperexcitability was observed in amygdalar neurons from kindled (included as a control for seizure activity) or control rats. Blockade of ionotropic glutamate receptors unmasked inhibitory postsynaptic potentials in epileptic pyramidal neurons. Control, kindled and epileptic inhibitory potentials were predominantly biphasic, with fast and slow components, but a few cells exhibited only the fast component (2/12 in controls, 0/3 in kindled, 3/10 in epileptic). Epileptic fast inhibitory potentials had a more rapid onset and shorter duration than control and kindled. Approximately 40% of control neurons exhibited spontaneous inhibitory potentials; no spontaneous inhibitory potentials were observed in neurons from kindled or epileptic rats. A preliminary histological examination revealed no gross alterations in the basal amygdala from epileptic animals. These results extend previous findings from this laboratory that hyperexcitability is found in multiple epileptic limbic regions and may be secondary to multiple alterations in excitatory and inhibitory efficacy. Because there were no differences between control and kindled animals, the changes observed in the epileptic animals are unlikely to be secondary to recurrent seizures.

Topics: Action Potentials; Amygdala; Animals; Disease Models, Animal; Electric Stimulation; Epilepsy; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; GABA Antagonists; Kindling, Neurologic; Neural Pathways; Neurons; Phosphinic Acids; Propanolamines; Quinoxalines; Rats; Valine

In humans with temporal lobe epilepsy and kainate-treated rats, the mossy fibers of the dentate granule cells send collateral axons into the inner molecular layer. Prior investigations on kainate-treated rats demonstrated that abnormal hilar-evoked events can occasionally be observed in slices with mossy fiber sprouting when gamma-aminobutyric acid-A (GABAA)-mediated inhibition is blocked with bicuculline. However, these abnormalities were observed infrequently, and it was unknown whether these rats were epileptic. Wuarin and Dudek reported that in slices from kainate-induced epileptic rats (3-13 mo after treatment), hilar stimulation evoked abnormal events in most slices with mossy fiber sprouting exposed simultaneously to bicuculline and elevated extracellular potassium concentration [K+]o. Using the same rats, extracellular recordings were obtained from granule cells in hippocampal slices to determine whether 1) hilar stimulation could evoke abnormal events in slices with sprouting in normal artificial cerebrospinal fluid (ACSF), 2) adding only bicuculline could unmask hilar-evoked abnormalities and glutamate-receptor antagonists could block these events, and 3) increasing only [K+]o could unmask these abnormalities. In normal ACSF, hilar stimulation evoked abnormal field potentials in 27% of slices with sprouting versus controls without sprouting (i.e., saline-treated or only 2-4 days after kainate treatment). In bicuculline (10 microM) alone, hilar stimulation triggered prolonged field potentials in 84% of slices with sprouting, but not in slices from the two control groups. Addition of the N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-amino-5-phosphonopentanoic acid (AP5), either blocked the bursts or reduced their probability of occurrence. The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), always eliminated the epileptiform bursts. In kainate-treated rats with sprouting, but not in saline-treated controls, abnormal hilar-evoked responses were also revealed in 6-9 mM [K+]o. Additionally, 63% of slices with sprouting generated spontaneous bursts lasting 1-40 s in ACSF containing 9 mm [K+]o; similar bursts were not observed in controls. These results indicate that 1) mossy fiber sprouting is associated with new glutamatergic pathways, and although NMDA receptors are important for propagation through these circuits, AMPA receptor activation is crucial, 2) modes

Topics: 2-Amino-5-phosphonovalerate; Animals; Bicuculline; Dentate Gyrus; Electric Stimulation; Electrophysiology; Epilepsy; Epilepsy, Temporal Lobe; Evoked Potentials; Excitatory Amino Acid Antagonists; GABA-A Receptor Antagonists; Humans; In Vitro Techniques; Kainic Acid; Male; Motor Activity; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, GABA-A; Reference Values

The time course of alteration in neuronal nitric oxide synthase (nNOS) and the influence of glutamate receptor antagonists on immunoreactivity of nNOS were investigated immunohistochemically in rat hippocampus during penicillin-induced epilepsy. It was found that nNOS-like immunoreactivity in hippocampus increased at 4 h after initiation of seizure and reached a peak at 24 h. When MK-801 (6 micrograms) and DNQX (4 micrograms) were injected respectively into hippocampus 20 min before administration of penicillin, seizure was reduced in strength. Meanwhile, the nNOS-like immunoreactivity in hippocampus was decreased, compared with the group which were administered penicillin alone. These results suggest that the increase of nitric oxide may be related to the injury of neurons during and after epilepsy; the changes' of nNOS may be related to the activity of NMDA and non-NMDA receptors. Neuron protective effect of MK-801 and DNQX may be in part mediated by nNOS.

Topics: Animals; Dizocilpine Maleate; Electroencephalography; Epilepsy; Excitatory Amino Acid Antagonists; Female; Hippocampus; Male; Penicillin G; Quinoxalines; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate

To study the effect of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and bicuculline (Bic) on benzyl-penicillin-induced-epilepsy (PIE) and electroacupuncture (EA) antiepilepsy in rats.. Epilepsy was elicited by intra-hippocampal microinjection of benzylpenicillin in rats. The analysis of electroencephalogram (EEG) and power spectrum was used to measure the extent of convulsion.. EA or DNQX (1 microgram) showed partial inhibitory effect on PIE. EA + DNQX caused further inhibition of PIE, and Bic attenuated EA antiepileptic effect.. Antagonization of GABA-A receptor attenuated EA antiepileptic effect, and EA acted synergistically with the antagonists of non-N-methyl-D-aspartate (non-NMDA) receptors.

Topics: Animals; Anticonvulsants; Bicuculline; Electroacupuncture; Electroencephalography; Epilepsy; Female; GABA Antagonists; Hippocampus; Male; Penicillin G; Quinoxalines; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate

1. Bicuculline-induced epileptiform bursts in slices of neocortical tissue resected from children (3 mo to 14 yr) undergoing neurosurgical treatment for intractable epilepsy were studied with conventional intracellular recording techniques. The purposes of this study were to characterize the bursts evoked in immature human neocortical slices, to gain further insight to how N-methyl-D-aspartate (NMDA) and non-NMDA receptors contribute to the genesis of the bursts, and to determine whether the characteristics of the bursts were related to patient age or clinically defined abnormality of the tissue. 2. Epileptiform bursts evoked by focal stimulation of the underlying white or gray matter in bicuculline (10 microM) were all-or-none events. Once evoked, the bursts in a given neuron appeared very similar to one another, regardless of stimulus intensity. Stronger stimuli only decreased the onset latency of the bursts. The bursts evoked with relatively weak stimuli (< 2-3 times the threshold), particularly those from stimulation of a distant site (4-5 mm), were variable in onset latency. The bursts from stimulation of a close site (0.5-2 mm) with stronger stimuli (> 3 times the threshold) were invariable in onset latency. 3. Across different cells, particularly across the cells in different slices, the bursts were quite variable in terms of their morphology and duration. When measured at one-half of the amplitude of the underlying depolarization (approximately 20-50 mV), the duration of the bursts ranged from 20 to 775 ms (n = 80 cells). In 23% of the cases (18 of 80 cells), afterdischarges lasting for tens of milliseconds to a few seconds followed the bursts.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 2-Amino-5-phosphonovalerate; Adolescent; Bicuculline; Cerebral Cortex; Child; Child, Preschool; Culture Techniques; Electric Stimulation; Electroencephalography; Epilepsy; Evoked Potentials; Female; Humans; Infant; Male; Neurons; Psychosurgery; Quinoxalines; Receptors, N-Methyl-D-Aspartate; Spasms, Infantile; Synaptic Transmission

1. The dentate gyrus has been proposed to be a gate for entry of neuronal activity into the hippocampus. This function would give it a critical role in the propagation of seizure activity in that region. The hallmark of epileptiform activity in the dentate itself, often referred to as "maximal dentate activation" (MDA), has not been reproduced previously in vitro. 2. With the use of rat hippocampal slices, bath [Ca2+] was decreased, and [K+] was increased concurrently to simulate conditions found during intense neuronal activity in vivo. Both evoked and spontaneous field bursts were observed in the dentate granule cell layer under these conditions. These bursts were similar to MDA, consisting of a prolonged negative shift in extracellular potential with large-amplitude population spikes. 3. In 0.5 mM bath [Ca2+], single stimuli applied to the perforant path could evoke prolonged field bursts in the dentate only when bath [K+] was > or = 9 mM. However, repetitive stimulation (10 Hz) of the perforant path could elicit similar dentate responses when bath [K+] was as low as 5 mM. 4. In 0.5 mM bath [Ca2+], interictal-type bursts appeared spontaneously in CA1 and CA3 when bath [K+] was > or = 5 mM but were lost when [K+] was > 9 mM. Spontaneous seizurelike activity in the dentate required a higher minimum bath [K+] (9 mM) and persisted at [K+] of 11 mM. 5. Stimulation-evoked field bursts in the dentate altered epileptiform activity in CA3. At bath [K+] insufficient to cause spontaneous CA3 bursts, CA3 was activated transiently when prolonged field bursts occurred in the dentate. At higher bath [K+] in which spontaneous CA3 bursts did occur, they were depressed during the dentate bursts. 6. Deletion of Ca2+ from the bath; the addition of 30 microM each of bicuculline methiodide, D,L-2-amino-5-phosphonopentanoate (AP-5), and 6,7-dinitroquinoxaline-2,3-dione (DNQX); or the combination of both manipulations did not block antidromically evoked or spontaneous prolonged field bursts in the dentate. Thus the mechanisms maintaining and propagating these events did not require fast amino acid-mediated synaptic transmission. 7. The concurrent alteration of [K+] and [Ca2+] required to produce prolonged field bursts in the dentate underscores the positive feedback relationship between neuronal excitation and extracellular ionic concentrations, whereas the ability of synaptic stimulation to trigger nonsynaptic seizurelike events such as these prolonged field bursts may be re

Topics: Amino Acids; Animals; Calcium; Electric Stimulation; Electrodes; Epilepsy; Female; Hippocampus; In Vitro Techniques; Male; Membrane Potentials; Neurons; Potassium; Quinoxalines; Rats; Rats, Sprague-Dawley; Synapses; Synaptic Transmission

The contribution of non-synaptic mechanisms to the seizure susceptibility of rat CA1 hippocampal pyramidal cells was examined in vitro by testing the effects of osmolality on synchronous neuronal activity, using solutions which blocked chemical synaptic transmission both pre- and post-synaptically. Decreases in osmolality, which shrink the extracellular volume, caused or enhanced epileptiform bursting. Increases in osmolality with membrane-impermeant solutes, which expand the extracellular volume, blocked or greatly reduced epileptiform discharges. Reductions in the extracellular volume, therefore, can enhance synchronization among CA1 hippocampal neurons through non-synaptic mechanisms. Since similar osmotic treatments are known to modify epileptiform discharges in several models of epilepsy, non-synaptic mechanisms are probably more important in hippocampal epileptogenesis than previously realized and may contribute to the high susceptibility of this brain region to epileptic seizures in animals and humans. These data also provide a possible explanation for the observation in humans that decreased plasma osmolality, which can be associated with a wide range of clinical syndromes, leads to seizures.

Topics: Action Potentials; Animals; Electric Stimulation; Epilepsy; Extracellular Space; Hippocampus; In Vitro Techniques; Neurons; Osmolar Concentration; Pyramidal Tracts; Quinoxalines; Rats; Synapses

1. Two quinozalinediones, FG9041 and FG9065, which had previously been shown to displace binding to the quisqualate receptor, were tested on rat neocortex and frog spinal cord in vitro against depolarizations induced by quisqualate, kainate and N-methyl-D-aspartate (NMDA). In both preparations effects of quisqualate were reduced the most and those of NMDA the least. 2. The near unitary slopes of the Schild plots were consistent with a competitive type of interaction. pA2 values for FG9041 were estimated to be 6.6, 6.1 and 5.1 in frog cord and 5.9, 5.3 and and about 4 in the rat neocortex for quisqualate, kainate and NMDA antagonism, respectively. FG9065 gave equivalent pA2 values of 6.2, 5.6 and 4.5. 3. At concentrations, which were without effect on depolarizations induced by NMDA, FG9041 and FG9065 reduced or blocked synaptically-evoked field potentials in hippocampal and neocortical slices superfused with normal magnesium-containing medium. Since these synaptic components are also insensitive to NMDA antagonists, these results are consistent with their mediation by postsynaptic receptors of the quisqualate (or kainate) type. 4. By contrast, quinoxalinediones had only limited effects on spontaneous epileptiform activity seen in both neocortical and hippocampal preparations when superfused with magnesium-free medium. These burst discharges were, however, abolished by NMDA antagonists. 5. In the frog spinal cord the early component of the dorsal root to ventral root reflexes was selectively reduced by FG9041 whereas NMDA antagonists reduced the longer latency components. 6. Our results suggest that the quinoxalinediones are likely to be useful pharmacological probes for elucidating the role of non-NMDA receptors in the vertebrate central nervous system.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Anura; Cerebral Cortex; Electric Stimulation; Epilepsy; Evoked Potentials; Hippocampus; In Vitro Techniques; Kainic Acid; Neuromuscular Depolarizing Agents; Oxadiazoles; Quinoxalines; Quisqualic Acid; Rats; Rats, Inbred Strains; Receptors, Kainic Acid; Receptors, Neurotransmitter; Spinal Cord; Synapses