Date of Award

6-2005

Document Type

Open Access Thesis

Degree Name

Master of Science (MS)

Department

Biotechnology and Biomedical Science

First Advisor

Alexia Pollack

Second Advisor

Kenneth L. Campbell

Third Advisor

Robert Stevenson

Abstract

An argument for levodopa induced dyskinesias (LID) as an expression of long term potentiation (LTP) in the striatum is presented. Normally, with an intact nigrostriatal dopamine (DA) input, long term depression (LTD) is expressed in the striatum, however, striatal LTD is lost following DA denervation and chronic levodopa treatment. It is possible that these changes in synaptic efficacy are due to two other chemical modulators, achetylcholine (ACh) and glutamate, which in turn leads to the induction of striatal LTP. ACh and glutamate may produce these changes in motor behavior by affecting the striosomal pathway in addition to their effect on the direct (striatonigral) pathway and the indirect (striatopallidal) pathway of the basal ganglia. This thesis postulates that by blocking LTP expression in the DA depleted striatum, that the occurrence of LID will be reduced. Heterosynaptic plasticity is a mechanism in which long-term facilitation proceeds in the state of LTD or LTP depending on the levels of intracellular calcium present. Artificial neural networks (ANN) may be used to speculate and predict the most accurate and precise combinations of levodopa, ACh antagonist and glutamate antagonists that will achieve the goal of preventing LTP in DA denervated and chronic levodopa treated biological systems to reduce/eliminate LID.

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