Objective: To employ behavioral test, positron emission tomography (PET) imaging and immunohistochemical staining to assess the changes of brain function and dopaminergic system in rat models of Parkinson’s disease (PD) induced by unilateral injection of 6-hydroxydopamine (6-OHDA) in MFB (medial forebrain bundle).

Background: Rats unilaterally lesioned with 6-OHDA have been used as a useful hemi-Parkinson model for studying dopamine (DA) -related functions and assessing treat ment of PD. PET is capable of repeated and quantitative measurements in Parkinsonian animal models.

Methods: Thirty healthy male Sprague-Dawley (SD) rats were randomly divided into PD modeling group (N = 22) and normal control group (N = 8). Rats in modeling group received stereotactically and unilaterally administered 6-OHDA in the right MFB with two points. Behavioral studies were carried out by apomorphine rotational test (>7 turns/min is a successful PD model) and Cylinder test (assessing forelimb function) in all lesioned rats 3-5 weeks after the surgical procedure. [18F]fluoro-deoxyglucose ([18F]FDG) and [11C]CFT PET were performed to assess brain function and dopamine transporter in both PD model and normal rats. Tyrosine hydroxylase (TH) immunohistochernical staining was used to detect the change of dopaminergic neurons in substantia nigra in PD rat models.

Results: There were 14 successful PD rat models (63.6% success rate). Apomorphine test induced remarkable left rotations in PD rat models, with an average number of 12.0 ± 2.7 turns / min. Cylinder test indicated total forelimb activities were significantly reduced in PD rat models (0.5 ± 0.3 rears/min) than control group (2.8 ± 0.8 rears/min). Asymmetric forelimb activities were significantly increased in PD rat models of (90.0%) than control group (10.7%). [18F]FDG PET imaging showed decreased glucose metabolism in the right sensorimotor cortex, striatum and hippocampus area of PD rat models, compared with that in normal rats. [11C]CFT PET imaging showed significantly decreased DAT binding in the lesion side of striatum of PD rat models. TH immunohistochemistry showed significantly reduced TH-positive cells in the lesion side of substantia nigra.

Conclusions: Unilateral injection of 6-OHDA in MFB can establish PD rat models with high success rate. [18F]FDG and [11C]CFT PET imaging, combining with behavioral observations, can be served as one of standards for PD model verification and a useful molecular imaging tool for basic and clinical research of PD.

References: 1.Nguyen VH, Verdurand M, Dedeurwaerdere S, et al. Increased brain metabolism after acute administration of the synthetic cannabinoid HU210: a small animal PET imaging study with 18F-FDG. Brain Res Bull 2012;87:172-179. 2.Sossi V, Dinelle K, Topping GJ, et al. Dopamine transporter relation to levodopa-derived synaptic dopamine in a rat model of Parkinson’s: an in vivo imaging study.J Neurochem 2009;109:85-92.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/behavior-and-pet-imaging-study-in-parkinsonian-rat-models-induced-by-injection-of-6-ohda-in-medial-forebrain-bundle/