MODEL OF PARKINSON'S DISEASE USING MPTP

Project Details

Description

The objective of the following studies is to rigorously evaluate the
behavioral deficits observed in the rodent model of Parkinson's Disease
using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Exposure to
MPTP caused parkinsonian-like symptoms in a number of individuals. This
observation has led to an intensive effort to develop animal models of
MPTP-induced toxicity in the hope of gaining insight into the etiology of
Parkinson's Disease. It is clear that the administration of MPTP to
subhuman primates causes the parkinsonian-like symptoms. However, initial
studies using rats and mice concluded that MPTP was without effect in these
species. One of the major issues was that there were no overt
parkinsonian-like behavioral symptoms observed in rodents following MPTP
administration. In this proposal, it is argued that MPTP does indeed
produce marked behavioral deficits in rodents but, more sensitive
behavioral paradigms are required to unmask these deficits. Among the advantages of using rodents rather than subhuman primates to
study MPTP-induced toxicity are substantially reduced expenses and the
wealth of data already available on rodent models of Parkinson's Disease.
For example, the classic work of Carlsson on the effects of 1-dopa in
reversing performance deficits of reserpinized mice in the shuttle box
paradigm led to the clinical trials of 1-dopa in Parkinson's Disease
patients. In preliminary studies, a substantial deficit in shuttle box
avoidance responding was observed in mice following the administration of
MPTP. The deficit was reversed by 1-dopa. Accordingly, the first
objective of the studies in this proposal is to replicate and extend these
initial findings in an attempt to systematically evaluate the behavioral
deficits following MPTP administration to rats. A second behavioral paradigm which has been employed for the analysis of
behavioral deficits associated with brain dopamine depletions is the force
lever paradigm. This paradigm provides a sensitive measure of the fine
motor control of the subject and serves as an excellent compliment to the
more molar behaviors assessed in the shuttle box. Accordingly, the second
objective of these studies is to determine if MPTP administration causes a
deficit in fine motor control of the rat. Conclusions concerning the utility of the rodent model of Parkinson's
Disease using MPTP can be made only after a rigorous and systematic
evaluation of the resulting behavioral deficits as measured in sensitive
behavioral paradigms.
StatusFinished
Effective start/end date4/1/863/31/88

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

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