PURPOSE: 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). PROCEDURES: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: Post-synaptic dopamine D2/3 receptors are reduced in animal models of obesity, and in obesehumans, 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). PROCEDURES: 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. RESULTS: 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. CONCLUSIONS: 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.
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