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Updated: Aug 8, 2026
Murine Model for Parkinson's Disease: from 6-OH Dopamine Lesion to Behavioral Test
Published on: January 15, 2010
Dopamine terminal loss and onset of motor symptoms in MPTP-treated monkeys: a positron emission tomography study with
U Wüllner1, P Pakzaban, A L Brownell
1Neuroregeneration Laboratories, McLean Hospital, Belmont, Massachusetts.
Abstract:
We studied the time course of dopamine (DA) terminal loss in three macaca fascicularis injected with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intravenously every 10-14 days for up to 389 days. Striatal DA terminal loss was monitored in vivo by positron emission tomography using 11C-CFT (WIN 35,428), a cocaine derivative that labels the DA transporter. The 11C-CFT uptake rate constant in the striatum of MPTP-treated monkeys decreased exponentially over time, with the putamen significantly more affected than the caudate. Spontaneous locomotor activity decreased in parallel with the decline of the 11C-CFT uptake rate; however, overt parkinsonian signs appeared only after the 11C-CFT uptake rate had declined to about 30% of the pretreatment values. We conclude that a long-term intermittent mode of administration of MPTP can lead to a pattern of terminal loss that closely resembles idiopathic Parkinson disease.
Insights
This study shows that long-term MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administration in monkeys causes dopamine terminal loss, mimicking Parkinson disease progression.
Area of Science:
- Neuroscience
- Primate Models
- Neurodegenerative Diseases
Background:
- Parkinson disease is characterized by progressive loss of dopamine (DA) neurons.
- Understanding the time course of DA terminal loss is crucial for developing effective treatments.
- MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin used to model Parkinson disease.
Purpose of the Study:
- To investigate the time course of dopamine terminal loss in Macaca fascicularis monkeys after chronic MPTP administration.
- To correlate dopamine transporter levels with behavioral changes and the onset of parkinsonian signs.
Main Methods:
- Three Macaca fascicularis monkeys were intravenously injected with MPTP every 10-14 days for up to 389 days.
- Striatal dopamine terminal loss was monitored using positron emission tomography (PET) with 11C-CFT (a dopamine transporter ligand).
- Spontaneous locomotor activity and overt parkinsonian signs were assessed.
Main Results:
- 11C-CFT uptake rate constant in the striatum decreased exponentially over time, indicating progressive dopamine terminal loss.
- The putamen was more severely affected than the caudate nucleus.
- Locomotor activity declined in parallel with dopamine transporter levels, but parkinsonian signs only emerged when uptake dropped to approximately 30% of baseline.
Conclusions:
- Long-term, intermittent MPTP administration in non-human primates creates a robust model for studying Parkinson disease.
- This model demonstrates a gradual loss of dopamine terminals that closely resembles the pattern seen in idiopathic Parkinson disease.
- The findings highlight a significant reserve capacity of motor function before overt parkinsonian symptoms manifest.
