Introduction This study aims to reveal the feasibility and potential of molecular connectivity based on neurotransmission in comparison with the metabolic connectivity with an application to dopaminergic pathways. For this purpose, we propose to compare the neurotransmission connectivity findings using 123 I-FP-CIT SPECT and 18 F-FDOPA PET with the metabolic connectivity findings using 18 F-FDG PET. Methods 18 F-FDG PET and 123 I-FP-CIT SPECT images from 47 subjects and 18 F-FDOPA PET images from 177 subjects, who had no neurological or psychiatric disorders, were studied. Interregional correlation analyses were performed at the group level to determine the midbrain’s connectivity via glucose metabolic rate using 18 F-FDG PET and via dopaminergic binding potential using 123 I-FP-CIT SPECT and 18 F-FDOPA PET. SPM-T maps of each radiotracer were generated, and masks used to highlight the significant differences obtained among the imaging modalities and targets. Results The three dopaminergic pathways (i.e., nigrostriatal, mesolimbic, and mesocortical) were identified by 18 F-FDG PET (1599 voxels, with a T max value of 12.6), 123 I-FP-CIT SPECT (1120 voxels, with T max value of 5.1), and 18 F-FDOPA PET (6054 voxels, with T max value of 11.7) for a T voxel threshold of 5.10, 2.80, and 5.10, respectively. Using the same T voxel threshold of 5.10, 18 F-FDOPA PET showed more specific findings than 18 F-FDG PET with less voxels identified outside these pathways (− 9323 voxels), whereas no significant voxels were obtained with 123 I-FP-CIT SPECT at this threshold. Conclusion The present study illustrates the feasibility and interest in using molecular connectivity with 18 F-FDOPA PET for dopaminergic pathways. Such analyses could be applied to specific diseases involving the dopaminergic system.