Perturbed Development of Striatal Dopamine Transporters in Fatty Versus Lean Zucker Rats: a Follow-up Small Animal PET Study.

Abstract

Post-synaptic dopamine D2/3 receptors are reduced in animal models of obesity, and in obese humans, concordant with similar findings in habitual drug users. However, corresponding pre-synaptic changes in brain dopamine are less documented in obesity models. Therefore, we used positron emission tomography (PET) with the dopamine transporter (DAT) ligand N-(3-[(18)F]fluoropropyl)-2-β-carbomethoxy-3-β-(4'-methylphenyl) tropane ([(18)F]FP-CMT) to test the hypothesis that DAT availability is attenuated in adult fatty Zucker (FZ) rats versus lean littermates (LZ). Groups of nine FZ and LZ rats were examined by [(18)F]FP-CMT PET at approximately 6 weeks and at 6 months of age. The baseline mean striatal binding potential (BPND) of [(18)F]FP-CMT did not differ between groups (LZ 2.4; FZ 2.5), although FZ rats already had higher body weight and elevated blood triglycerides, cholesterol, and insulin. At follow-up, a mixed effects multiple regression model showed that the maturation of DAT availability was attenuated in FZ rats, such that the mean BPND in striatum was 17 % lower (LZ 4.0; FZ 3.3; p = 0.01). Body weight was twofold higher in the adult FZ rats, and triglycerides fourfold increased, but glucose remained normal despite doubling of insulin levels. Maturation of the striatal dopamine innervation is impaired in this model of obesity/hyperlipidaemia without diabetes, implying an acquired trait of reduced dopamine reuptake capacity.