Antiepileptogenic and anticonvulsant effects of NBQX, a selective AMPA receptor antagonist, in the rat kindling model of epilepsy

Namba, Tatsuji; Morimoto, Kiyoshi; Satô, Keiko; Yamada, Norihito; Kuroda, Shigetoshi

doi:10.1016/0006-8993(94)90630-0

Cited by 98 publications

(44 citation statements)

References 39 publications

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“…CGP 39551 also prevented the induction of LTP in the hippocampal CA1 area after HFS of Schaffer collaterals (Maren et al, 1992), but had no noticeable effects on the monosynaptic fEPSP evoked in the CA1 area by single pulses presented to the ipsilateral Schaffer collaterals. In contrast, the fEPSP evoked in CA1 was attenuated by NBQX, a selective and competitive AMPA-receptor antagonist (Parada et al, 1992;Namba et al, 1994), indicating that CA3-CA1 synapses are normally activated by the opening of AMPA channels.…”

Section: General Remarksmentioning

confidence: 92%

Involvement of the CA3–CA1 Synapse in the Acquisition of Associative Learning in Behaving Mice

Gruart¹,

Muñoz²,

2006

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One of the brain sites more directly related with learning and memory processes is the hippocampus. We recorded, in conscious mice, the activity-dependent changes taking place at the hippocampal CA3-CA1 synapse during the acquisition, extinction, recall, and reconditioning of an associative task. Mice were classically conditioned to evoke eyelid responses using a trace [conditioned stimuli (CS), tone; unconditioned stimuli (US), shock] paradigm. A single electrical pulse presented to the Schaffer collateral-commissural pathway during the CS-US interval evoked a monosynaptic field EPSP (fEPSP) at ipsilateral CA1 pyramidal cells. The slope of evoked fEPSPs increased across conditioning sessions and decreased during extinction, being linearly related to learning evolution. In contrast, fEPSPs were not modified when evoked in control mice in the absence of a conditioning protocol. Long-term potentiation (LTP) evoked by high-frequency stimulation of Schaffer collaterals prevented acquisition, extinction, recall, or reconditioning, depending on the moment when it was triggered. Learning and memory impairments evoked by LTP induction resulted probably from the functional saturation of the CA3-CA1 synapse, although an additional disturbance of the subsequent information transfer toward postsynaptic circuits cannot be discarded. CGP 39551 [(E)-(Ϯ)-2-amino-4-methyl-5-phosphono-3-pentenoic acid ethyl ester](an NMDA antagonist) prevented LTP induction in behaving mice, as well as the acquisition of an eyelid learned response, and the synaptic changes taking place at the CA3-CA1 synapse across conditioning. In conclusion, the responsivity of the CA3-CA1 synapse seems to be modulated during associative learning, and both processes are prevented by experimental LTP or NMDA-receptor inactivation. Our results provide evidence of a relationship between activity-dependent synaptic plasticity and associative learning in behaving mice.

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Section: General Remarksmentioning

confidence: 92%

Involvement of the CA3–CA1 Synapse in the Acquisition of Associative Learning in Behaving Mice

Gruart¹,

Muñoz²,

2006

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“…Body temperatures were maintained at 37°C for 6 hours after the initiation of occlusion, and CP-465,022 had minimal effects on other physiological parameters during this period. Twenty-four hours after the initiation of occlusion, the volume of cortical infarction was 141Ϯ46 mm 3 (meanϮSD) in vehicle-treated animals ( Figure 4). CP-465,022 caused a small decrease in infarct volume (to 124Ϯ49 mm 3 ), but this was not significantly different from the vehicle control group.…”

Section: Focal Ischemiamentioning

confidence: 99%

“…Twenty-four hours after the initiation of occlusion, the volume of cortical infarction was 141Ϯ46 mm 3 (meanϮSD) in vehicle-treated animals ( Figure 4). CP-465,022 caused a small decrease in infarct volume (to 124Ϯ49 mm 3 ), but this was not significantly different from the vehicle control group. A second group of 4 animals received a higher dose of CP-465,022 (10 mg/kg SC) under identical conditions; however, these animals all died within 1 hour of compound administration.…”

Section: Focal Ischemiamentioning

confidence: 99%

“…Rats were placed into chambers (30 cm 3 ) equipped with photocells housed in sound-attenuating cabinets. Compounds were administered to unhabituated animals immediately before placement into chambers, and horizontal (crossovers) and vertical (rears) locomotion was recorded for 12 hours.…”

Section: Spontaneous Locomotor Activitymentioning

confidence: 99%

“…While the initial focus was on compounds that inhibit N-methyl-D-aspartate (NMDA) receptors, there has also been interest in ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. 1 This interest stems largely from studies with the prototype AMPA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX) 2 and structurally related analogues such as 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione hydrochloride (YM-90K) 3 and [1,2,3,4-tetrahydro-7-morpholinyl-2,3-dioxo-6-(trifluoromethyl)quinoxalin-1-yl]methanephosphonate (ZK-700,775). 4 These compounds effectively reduce the neuronal loss caused by ischemia and traumatic brain injury under a variety of experimental conditions.…”

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confidence: 99%

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CP-465,022, a Selective Noncompetitive AMPA Receptor Antagonist, Blocks AMPA Receptors but Is Not Neuroprotective In Vivo

Menniti

Buchan²,

Chenard³

et al. 2003

Stroke

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Background and Purpose-␣-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor inhibition has been hypothesized to provide neuroprotective efficacy after cerebral ischemia on the basis of the activity in experimental ischemia models of a variety of compounds with varying selectivity for AMPA over other glutamate receptor subtypes. CP-465,022 is a new, potent, and selective noncompetitive AMPA receptor antagonist. The present study investigated the ability of this compound to reduce neuronal loss after experimental cerebral ischemia to probe the neuroprotective potential of AMPA receptor inhibition. Methods-To demonstrate that CP-465,022 gains access to the brain, the effects of systemic administration of CP-465,022were investigated on AMPA receptor-mediated electrophysiological responses in hippocampus and on chemically induced seizures in rats. The compound was then investigated for neuroprotective efficacy in rat global and focal ischemia models at doses demonstrated to be maximally effective in the electrophysiology and seizure models. Results-CP-465,022 potently and efficaciously inhibited AMPA receptor-mediated hippocampal synaptic transmission and the induction of seizures. However, at comparable doses, CP-465,022 failed to prevent CA1 neuron loss after brief global ischemia or to reduce infarct volume after temporary middle cerebral artery occlusion. Conclusions-Given

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Selective reduction of GluR2 protein in adult hippocampal CA3 neurons following status epilepticus but prior to cell loss

Friedman

1998

Hippocampus

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Kainic acid (KA) induces status epilepticus and delayed neurodegeneration of CA3 hippocampal neurons. Downregulation of glutamate receptor 2 (GluR2) subunit mRNA [the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid (AMPA) subunit that limits Ca2+ permeability] is thought to a play role in this neurodegeneration, possibly by increased formation of Ca2+ permeable AMPA receptors. The present study examined early hippocampal decreases in GluR2 mRNA and protein following kainate‐induced status epilepticus and correlated expression changes with the appearance of dead or dying cells by several histological procedures. At 12 h, in situ hybridization followed by emulsion dipping showed nonuniform decreases in GluR2 mRNA hybridization grains overlying morphologically healthy‐appearing CA3 neurons. GluR1 and N‐methyl‐D‐aspartate receptor mRNAs were unchanged. At 12–16 h, when little argyrophilia or cells with some features of apoptosis were detected by silver impregnation or electron microscopy, single immunohistochemistry with GluR2 and GluR2/3 subunit‐specific antibodies demonstrated a pattern of decreased GluR2 receptor protein within CA3 neurons that appeared to predict a pattern of damage, similar to the mRNA observations. Double immunolabeling showed that GluR2 immunofluorescence was depleted and that GluR1 immunofluorescence was sustained in clusters of the same CA3 neurons. Quantitation of Western blots showed increased GluR1:GluR2 ratios in CA3 but not in CA1 or dentate gyrus subfields. Findings indicate that the GluR1:GluR2 protein ratio is increased in a population of CA3 neurons prior to significant cell loss. Data are consistent with the “GluR2 hypothesis” that reduced expression of GluR2 subunits will increase formation of AMPA receptors permeable to Ca2+ and predict vulnerability to a particular subset of pyramidal neurons following status epilepticus. Hippocampus 1998;8:511–525. © 1998 Wiley‐Liss, Inc.

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Antiepileptogenic and anticonvulsant effects of NBQX, a selective AMPA receptor antagonist, in the rat kindling model of epilepsy

Cited by 98 publications

References 39 publications

Involvement of the CA3–CA1 Synapse in the Acquisition of Associative Learning in Behaving Mice

Involvement of the CA3–CA1 Synapse in the Acquisition of Associative Learning in Behaving Mice

CP-465,022, a Selective Noncompetitive AMPA Receptor Antagonist, Blocks AMPA Receptors but Is Not Neuroprotective In Vivo

Selective reduction of GluR2 protein in adult hippocampal CA3 neurons following status epilepticus but prior to cell loss

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