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Role of Glutamate Release and Metabotropic Autoreceptors in Seizureogenic Actions of Cholinomimetric Agents.

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Annual rept. 1 Oct 98-30 Sep 99

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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 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.

Subject Categories:

  • Psychology
  • Biochemistry
  • Anatomy and Physiology

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