Project Details


The studies in this proposal are designed to determine if slight,
presymptomatic lesions of the brain dopaminergic and/or
serotonergic neurons can be assessed (i.e. unmasked) through the
use of sensitive behavioral paradigms combined with drug
challenge. Long-Evans rats will be used as subjects and they will
be treated with the systemically administered neurotoxins 1-
methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or
methamphetamine. By varying the dose of these toxins, the
magnitude of the lesion can be varied. The lesion magnitude for
the dopaminergic system will range from 0% (i.e. control) to a
maximum 75% depletion. These dopaminergic lesions will be
accompanied by serotonergic lesions (simultaneously induced by
both toxins) ranging in magnitude from 0% up to approximately
60% depletion. Both of these toxins have proven invaluable in
advancing our understanding of the factors which lead to the
degeneration of central dopaminergic and serotonergic neurons
and, as such, have served as excellent models of Parkinson's
disease. However, the use of rodents to explore these models has
been somewhat restricted by the failure to demonstrate
behavioral deficits associated with the toxin-induced damage. In
this regard, however, the PI has obtained some degree of success
stemming from use of carefully chosen behavioral paradigms used
in conjunction with drug challenge tests. The demonstration that
rodents with MPTP or methamphetamine-induced dopaminergic
lesions do exhibit behavioral deficits has provided support for the
validity of these models.
Effective start/end date12/31/893/31/92


  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke


  • Medicine(all)
  • Neuroscience(all)
  • Clinical Neurology
  • Neurology


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