Effect of Dopamine D Receptor Antagonists on [F]-FEOBV Binding.

The interaction of dopaminergic and cholinergic neurotransmission in, e.g., Parkinson's disease has been well established. Here, D receptor antagonists were used to assess changes in [F]-FEOBV binding to the vesicular acetylcholine transporter (VAChT) in rodents using positron emission tomography (PET). After pretreatment with either 10 mg/kg haloperidol, 1 mg/kg raclopride, or vehicle, 90 min dynamic PET scans were performed with arterial blood sampling. The net influx rate () was obtained from Patlak graphical analysis, using a metabolite-corrected plasma input function and dynamic PET data. [F]-FEOBV concentration in whole-blood or plasma and the metabolite-corrected plasma input function were not significantly changed by the pretreatments (adjusted > 0.07, Cohen's 0.28-1.89) while the area-under-the-curve (AUC) of the parent fraction of [F]-FEOBV was significantly higher after haloperidol treatment (adjusted = 0.022, Cohen's = 2.51) than in controls. Compared to controls, the AUC of [F]-FEOBV, normalized for injected dose and body weight, was nonsignificantly increased in the striatum after haloperidol (adjusted = 0.4, Cohen's = 1.77) and raclopride (adjusted = 0.052, Cohen's = 1.49) treatment, respectively. No changes in the AUC of [F]-FEOBV were found in the cerebellum (Cohen's 0.63-0.74). Raclopride treatment nonsignificantly increased in the striatum 1.3-fold compared to control rats (adjusted = 0.1, Cohen's = 1.1) while it reduced in the cerebellum by 28% (adjusted = 0.0004, Cohen's = 2.2) compared to control rats. Pretreatment with haloperidol led to a nonsignificant reduction in in the striatum (10%, adjusted = 1, Cohen's = 0.44) and a 40-50% lower than controls in all other brain regions (adjusted < 0.0005, Cohen's = 3.3-4.7). The changes in induced by the selective D receptor antagonist raclopride can in part be quantified using [F]-FEOBV PET imaging. Haloperidol, a nonselective D/σ receptor antagonist, either paradoxically decreased cholinergic activity or blocked off-target [F]-FEOBV binding to σ receptors. Hence, further studies evaluating the binding of [F]-FEOBV to σ receptors using selective σ receptor ligands are necessary.