[(18)F]fallypride-PET/CT Analysis of the Dopamine D(2)/D(3) Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection.

Authors：Mann Teresa^*; Kurth Jens^*; Hawlitschka Alexander^*; Stenzel Jan^*; Lindner Tobias^*; Polei Stefan^*; Hohn Alexander^*; Krause Bernd J^*; Wree Andreas^*

Source：Molecules, 2018, 23(3).

DOI：10.3390/molecules23030587

• Botulinum neurotoxin A
• D2/D3 receptors
• MRI
• PET/CT
• Parkinson's disease
• [18F]fallypride
• basal ganglia
• hemiparkinsonian rat model
• small animal imaging
• striatum

Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson's disease. The caudate-putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and directly interacts with the dopaminergic system. To determine receptor-mediated explanations for the BoNT-A effect, we analyzed the dopamine D(2)/D(3) receptor (D(2)/D(3)R) in the CPu of 6-hydroxydopamine (6-OHDA)-induced hemi-PD rats by [(18)F]fallypride-PET/CT scans one, three, and six months post-BoNT-A or -sham-BoNT-A injection. Male Wistar rats were assigned to three different groups: controls, sham-injected hemi-PD rats, and BoNT-A-injected hemi-PD rats. Disease-specific motor impairment was verified by apomorphine and amphetamine rotation testing. Animal-specific magnetic resonance imaging was performed for co-registration and anatomical reference. PET quantification was achieved using PMOD software with the simplified reference tissue model 2. Hemi-PD rats exhibited a constant increase of 23% in D(2)/D(3)R availability in the CPu, which was almost normalized by intrastriatal application of BoNT-A. Importantly, the BoNT-A effect on striatal D(2)/D(3)R significantly correlated with behavioral results in the apomorphine rotation test. Our results suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing interhemispheric changes of striatal D(2)/D(3)R.

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