# DOPAMINERGIC NEUROTOXINS AND AGING

> **NIH NIH R01** · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · 1992 · $130,803

## Abstract

Neurodegenerative disorder, such as Alzheimer's Disease and Parkinson's
Disease (PD), afflict a large number of our elderly population.  PD is a
neurodegenerative disease of unknown etiology characterized by a massive
loss of nigrostriatal dopaminergic neurons.  Recently, several young
individuals developed a Parkinsonian syndrome following the inadvertent
self-administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP).  Indeed, the administration of MPTP to experimental animals
results in damage to nigrostriatal dopaminergic neurons.  These findings
have led to the hypothesis that MPTP-like compounds may be responsible
for the neurodegeneration of dopaminergic neuron in idiopathic PD.
However, damage to nigrostriatal dopaminergic neurons in experimental
animals can also be produced by the administration of methamphetamine
(METH).  The mode of action of METH differs from that of MPTP.  Whereas
the neurotoxic action of MPTP  depend on the formation and action of its
metabolite, MPP+, those of METH appear to depend on the actions and/or
presence of the endogenous neurotransmitter, dopamine (DA).  The
possibility that DA itself may cause neurodegeneration has important
implications for PD.  The overall aims of this research project are to
compare and contrast the neurotoxic actions of various dopaminergic
neurotoxins, including MPTP, several of its analogs, and METH by
measuring biochemical markers of dopaminergic function (i.e., DA and
metabolite levels, tyrosine hydroxylase activity, DA transport
capacity).  Pharmacological agents which block enzymes, transport
systems and receptors will be used to elucidate similarities and
differences in the modes of action of the neurotoxins.  A second and
very important goal is to determine if older mice are more sensitive
than younger mice to these various neurotoxins and if so, what might
account for these age-related differences in sensitivity.  A third goal
is to determine if and how excitatory amino acids, which are involved
with neurodegeneration in a variety of disorders, might contribute to
dopaminergic cell death and whether or not there are age related
differences in their excitotoxic actions.  An overall goal underlying
this entire  project is to determine if there are similarities in the
etiology of idiopathic Parkinson's Disease in humans.

## Key facts

- **NIH application ID:** 3120124
- **Project number:** 5R01AG008479-04
- **Recipient organization:** UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
- **Principal Investigator:** Patricia K Sonsalla
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $130,803
- **Award type:** 5
- **Project period:** 1989-08-01 → 1993-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3120124

## Citation

> US National Institutes of Health, RePORTER application 3120124, DOPAMINERGIC NEUROTOXINS AND AGING (5R01AG008479-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3120124. Licensed CC0.

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