Role of Glutamate Release and Metabotropic Autoreceptors in Seizureogenic Actions of Cholinomimetic Agents
Final rept. 01 Oct 1998- 30 Sep 2001
FLORIDA UNIV GAINESVILLE
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The purpose of this project was to delineate the potential roles of excitatory amino acids EAA as mediators of central nervous system CNS excitation and seizures produced by centrally-active cholimomimetic agents and to evaluate possible palliative treatments for central cholimomimetic toxicity. The scope of this project entails simultaneous use of neurochemical and electrophysiological approaches that are designed to assess cholimomimetic-induced excitation in the rat CNS. The goals for this report period were 1 to evaluate simultaneously the effects by a direct acting cholimomimetic agent on basal and stimulus-dependent changes in hippocampal EAA levels as well as focal EEG activity, 2 to evaluate simultaneously the effects by an indirect acting cholimomimetic agent on basal and stimulus-dependent changes in hippocampal EAA levels as well as focal EEG activity, and 3 to evaluate the capacity of metabotropic glutamate autoreceptor ligands to attenuate the electrophysiological and neurochemical changes induced by agents referenced in goals 1 and 2. The described studies have been completed and the experimental results support the following general conclusions 1 elicitation of seizure-like brain wave activity by cholimomimetic agents does not arise principally from a global facilitation of excitatory amino acid mediated neurotransmission within major forebrain pathways and 2 agents that interact selectively with metabotropic glutamate receptors in the forebrain do not ameliorate substantially the excitatory actions of centrally-active cholimomimetic agents.
- Anatomy and Physiology
- Medicine and Medical Research