Role of Glutamate Release and Metabotropic Autoreceptors in Seizureogenic Actions of Cholinomimetric Agents.
Abstract
The purpose of this project is to delineate the potential role(s) 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 assemble a new on-line microdialysis instrument for rapid measurement of L-glutamate (GLU) and L-aspartate (ASP) in brain extracellular fluid, (2) to characterize the regulation of EAA levels by metabotropic GLU autoreceptors, and (3) to undertake preliminary studies of EAA levels in CNS tissues of cholinomimetic-treated rats. The first goal has been achieved insofar as the instrument has been assembled and validated in vivo. The second goal has been achieved and results demonstrate profound differences between striatum and hippocampus with respect to the efficiency of metabotropic GLU autoreceptor control over EAA levels. On-going studies related to the third goal have revealed that cholinomimetic agents produce differential and time-dependent changes in GLU and ASP levels in these brain regions. As planned, these studies will continue during year two.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA371386
Entities
People
- Thomas Vickory
Organizations
- University of Florida