The neurotoxicity of 3 non-NMDA glutamate receptor agonists--kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), and quisqualate--was investigated quantitatively in dissociated murine cortical cultures. Five minute exposure to 500 microM kainate, but not AMPA, produced widespread acute neuronal swelling. Kainate-induced swelling was resistant to 2-amino-5-phosphonovalerate (A...

N-methyl-d-aspartic acid (NMDA) receptors are critical for both normal brain functions and the pathogenesis of schizophrenia. We investigated the functional changes of glutamatergic receptors in the pyramidal cells and fast-spiking (FS) interneurons in the adolescent rat prefrontal cortex in MK-801 model of schizophrenia. We found that although both pyramidal cells and FS interneurons were affe...

in vivo microdialysis was used to study the effects of morphine on glutamate release from the ventral tegmentum area (vta) in freely moving rats. intraperitoneal (i.p.) injection of acute and repeated morphine at increasing doses significantly enhanced glutamate release. only a minor tolerance developed to this dosage of morphine. ap-s (2-amino-5-phosphonovaleric acid, 0.5 mg/kg i.p.), a nmda r...

NMDA and non-NMDA (AMPA/kainate) antagonists have potential in the treatment of a diverse group of neurological disorders associated with excessive activation of excitatory amino acid receptors. Here Michael Rogawski reviews recent progress in the development of therapeutically useful NMDA receptor channel blockers and a new class of selective AMPA/kainate receptor antagonists, the 2,3-benzodia...

Many central neurons receive inputs that are filtered by a variety of synaptic types with very different time constants. We study the response properties of a leaky integrate-and-fire (LIF) model neuron in the presence of both fast AMPA and slow NMDA filters and find an analytical formula valid when the membrane time constant τm of the neuron is short. When the NMDA/AMPA abundances are similar ...

Electrophysiological and pharmacological methods were used to examine the role of glutamate in mediating the excitatory and inhibitory responses produced by the N2v rasp phase neurons on postsynaptic cells of the Lymnaea feeding network. The N2v --> B3 motor neuron excitatory synaptic response could be mimicked by focal or bath application of -glutamate at concentrations of >/=10(-3) M. Quisqua...

The excitatory amino acid receptor (EAAR) types involved in the generation of light-evoked excitatory postsynaptic currents (EPSCs) were examined in X-type retinal ganglion cells. Using isolated and sliced preparations of cat and ferret retina, the light-evoked EPSCs of X cells were isolated by adding picrotoxin and strychnine to the bath to remove synaptic inhibition. N-methyl-D-aspartate (NMD...

The actions of the putative quisqualate-selective agonist DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) were examined in identified embryonic chick motoneurons using gigaseal recording techniques and compared with properties of the selective non-NMDA excitatory amino acid agonists kainate and quisqualate. Pressure application of AMPA induces an inward going current when ne...

Converging clinical and preclinical evidence has shown that dysfunction of the glutamate system is a core feature major depressive disorder. In this context, N-methyl-d-aspartate (NMDA) receptor antagonist ketamine raised growing interest as fast acting antidepressant. Using chronic mild stress (CMS) rat model depression, performed in male rats, we aimed at analyzing whether hippocampal specifi...

We examined the role of glutamatergic mechanisms in acute injury to rat spinal cord white matter. Compound action potentials (CAPs) were recorded from isolated dorsal column segments in vitro. Under control conditions (Ringer's solution), the CAPs decreased to 71.4 +/- 2.0% of preinjury values after compression injury with a clip exerting a closing force of 2 g. The combination of the NMDA rece...