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Updated: May 2, 2026
Murine Model for Parkinson's Disease: from 6-OH Dopamine Lesion to Behavioral Test
Published on: January 15, 2010
Relation between microPET imaging and rotational behavior in a parkinsonian rat model induced by medial forebrain
Limin Liu1, Wenzhong Zhang2, Xiaoli Gong2
1Department of Physiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China.
Abstract:
The purpose of the current study was to examine the relation between apomorphine (APO) induced rotational behavior and the pre- and post-synaptic dopaminergic function in a parkinsonian rat model induced by medial forebrain bundle (MFB) axotomy. The brains of these rats were unilaterally lesioned by mechanical transection of the nigrostriatal dopamine pathway at the MFB. Behavioral studies were carried out by APO challenge prior to and 1, 3, and 5 weeks after MFB axotomy. MicroPET scans with [(11)C]CFT and [(11)C]raclopride were performed 2 days after the behavioral test. The two PET scans were separated by an interval of 24-48 h. Immunohistochemistry was conducted 4 days after the last PET scan. Our data showed that [(11)C]CFT binding decreased progressively 1, 3, and 5 weeks postlesion, and there was a significant nonlinear correlation between [(11)C]CFT uptake ratio (right/left) and APO induced rotations. In contrast, [(11)C]raclopride binding only increased significantly 3 weeks postlesion, and there was a positive linear correlation between [(11)C]raclopride uptake ratio (right/left) and APO induced rotations. Postmortem immunohistochemical studies confirmed the loss of both striatal dopamine fibers and nigral neurons on the lesioned side. These findings not only demonstrate the relation between APO induced rotational behavior and the pre- and post-synaptic dopamine function but also indicate the utility and validity of in vivo PET imaging in understanding disease mechanisms and progression, which should in turn lead to development of new therapies.
Insights
Apomorphine-induced rotation in a rat model of Parkinson's disease correlates with both presynaptic dopamine transporter availability and postsynaptic dopamine D2 receptor density, as visualized by PET imaging.
Area of Science:
- Neuroscience
- Pharmacology
- Medical Imaging
Background:
- Parkinson's disease is characterized by the loss of dopaminergic neurons.
- Apomorphine (APO) challenge is used to assess dopaminergic function in parkinsonian models.
- Medial forebrain bundle (MFB) axotomy creates a unilateral parkinsonian rat model.
Purpose of the Study:
- To investigate the relationship between apomorphine-induced rotational behavior and pre- and post-synaptic dopaminergic function.
- To evaluate the utility of in vivo Positron Emission Tomography (PET) imaging in a rat model of Parkinson's disease.
Main Methods:
- Unilateral MFB axotomy in rats to induce a parkinsonian model.
- Apomorphine (APO) challenge tests at multiple time points post-lesion.
- MicroPET imaging using [(11)C]CFT (dopamine transporter) and [(11)C]raclopride (dopamine D2 receptors).
- Postmortem immunohistochemistry to confirm neuronal and fiber loss.
Main Results:
- [(11)C]CFT binding decreased progressively post-lesion, correlating non-linearly with APO-induced rotations.
- [(11)C]raclopride binding increased significantly at 3 weeks post-lesion, correlating linearly with APO-induced rotations.
- Immunohistochemistry confirmed nigrostriatal pathway degeneration.
Conclusions:
- Apomorphine-induced rotational behavior reflects both presynaptic and postsynaptic dopaminergic deficits in Parkinson's disease models.
- In vivo PET imaging is a valid tool for assessing disease progression and therapeutic targets.
- This study supports the development of novel Parkinson's disease therapies.
