ly382884 and Seizures

ly382884 has been researched along with Seizures* in 1 studies

Other Studies

1 other study(ies) available for ly382884 and Seizures

ArticleYear
Increased sensitivity to kainic acid in a genetic model of reduced NMDA receptor function.
    Brain research, 2010, Jan-11, Volume: 1307

    The pathophysiology of schizophrenia may involve reduced NMDA receptor function and experimental models of NMDA receptor hypofunction have proven useful for characterizing neurobiological abnormalities potentially relevant to schizophrenia. The present study assessed behavioral responses and induction of Fos after administration of kainic acid to wild type mice (NR1(+/+)) and mice with genetically reduced NMDA receptor expression (NR1(neo/neo)). At a dose of 20 mg/kg, kainic acid induced lethal seizures in 100% of the NR1(neo/neo) mice tested but produced no lethal seizures in the wild type mice. The NR1(neo/neo) mice also exhibited enhanced behavioral responses to kainic acid at a dose of 15 mg/kg but no lethal seizures were produced by this dose. A greater induction of Fos was observed in neocortical and limbic cortical regions of the NR1(neo/neo) compared to NR1(+/+) mice after administration of 15 mg/kg kainic acid. In contrast, there were no differences between the genotypes in kainic acid induced Fos in the amygdala, hippocampus, lateral septum, and nucleus accumbens. In order to determine if altered behavioral phenotypes of the NR1(neo/neo) mice could be related to increased sensitivity of kainate receptors to endogenous glutamate, effects of the highly selective kainate antagonist LY382884 were examined. The kainate antagonist reduced the exaggerated acoustic startle responses, deficits in prepulse inhibition of acoustic startle, and motor hyperactivity in the NR1(neo/neo) mice. These findings suggest that selective kainate receptor antagonists could be novel therapeutic candidates for schizophrenia.

    Topics: Acoustic Stimulation; Animals; Behavior, Animal; Brain; Disease Models, Animal; Excitatory Amino Acid Agonists; Exploratory Behavior; Female; Glutamic Acid; Isoquinolines; Kainic Acid; Male; Mice; Mice, Transgenic; Models, Genetic; Neural Inhibition; Oncogene Proteins v-fos; Receptors, N-Methyl-D-Aspartate; Reflex, Startle; Seizures

2010