Role of Glutamate Release and Metabotropic Autoreceptors in Seizureogenic Actions of Cholinomimetic Agents

The purpose of this project is to delineate the potential roles of excitatory amino acids EAA as mediators of central nervous system CNS excitation and seizures produced by centrally-active cholinomimetic agents and to evaluate possible palliative treatments for central cholinomimetic toxicity. The scope of this project entails simultaneous use of neurochemical and electrophysiological approaches that are designed to assess cholinomimetic-induced excitation in the rat CNS. The goals for this report period were 1 to establish and validate appropriate electroencephalographic EEG recording methods for measuring brain activities in anesthetized rats and to utilize these measures as an electrophysiological index of cholinomimetic-induced seizures, 2 to assess the temporal relationship between changes in EEG activity and extracellular levels of hippocampal excitatory amino acids EAA in response to systemic treatment or local intracerebral infusion of cholinomimetic agents, and 3 to undertake preliminary studies of the interaction between cholinomimetic agents and metabotropic glutamate autoreceptor ligands on EEG activity and extracellular EAA levels. The first two goals have been achieved insofar as we have demonstrated high-frequency brain wave activity following intravenous injection or intrahippocampal infusion of pilocarpine. Efforts related to the third goal are underway. These studies will continue into year three.