Seizures induced by microperfusion of glutamate and glycine in the hippocampus of rats pretreated with latrunculin A.
Changes in the membrane distribution of N-methyl-D-aspartate (NMDA) glutamate receptors seem to produce dramatic modifications in neuronal excitability and other properties of the neuron. In order to determine in vivo if these effects are due to the binding of extracellular glutamate and glycine to NMDA extrasynaptic receptors, we perfused the hippocampus of freely moving rats with the actin depolymerizant agent latrunculin A (4 microM) through microdialysis probes. One month later, continuous microperfusion of glutamate (1 mM) or glycine (1 mM) was used to induce epileptic seizures in the animals pretreated with latrunculin A. Glutamate microperfusion induced seizures in 50% of the animals studied, and glycine induced seizures in 75% of the rats. However, no effect was observed on control rats, or on those animals previously treated with picrotoxin. Simultaneous microperfusion of 100 microM MK-801 significantly reduced the number and duration of seizures induced by both glutamate and glycine. This study demonstrates that the application of latrunculin A results in long-term changes in susceptibility to the epileptogenic action of glutamate and glycine.
Vázquez-López
Araceli
A
Neuroscience Division, Department of Biochemistry and Molecular Biology, School of Medicine, University of Santiago, 15782 Santiago de Compostela, Spain.
Sierra-Paredes
Germán
G
Sierra-Marcuño
Germán
G
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D005998:Glycine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D013844:Thiazoles; D053778:Thiazolidines; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C037067:latrunculin A; D005998:Glycine