Pramipexole is a synthetic aminobenzothiazole derivative with selective actions mainly on D2 and D3 receptors, and it binds with the highest affinity to D3 receptors. In the brain, the distribution of D3 receptors is known to be different from that of D2 receptors, although there are some differences in the relative proportion of D2 and D3 receptors between the previous studies. The D2 binding sites are widely detected with the highest concentration found in the striatum, followed by the nucleus accumbens, external segment of the globus pallidus, substantia nigra and ventral tegmental area. The distribution of D3 receptors is relatively restricted and D3 binding sites are enriched in the amygdala, nucleus accumbens, ventral striatum, substantia nigra, anteroventral nucleus of the thalamus and internal segment of the globus pallidus. Thus, D2 or D3 binding sites are located in the synapse of the afferent structures as well as the neurons of the efferent structures such as substantia nigra and ventral tegmental area. D2 or D3 receptors in the efferent structures are thought to act as autoreceptors, which could play an important role in regulating the activity of dopaminergic neurons. On the other hand, in this study, the BPND in the substantia nigra or ventral tegmental area could not be quantified with reliability, because the structures were too small for usual ROI analysis of the dynamic data on the basis of the resolution of the PET scanner and the number of subjects was relatively small. For the same reasons, the ROIs were drawn over not each small nucleus but medial and lateral parts of the thalamus although the thalamus is known to have a great deal of regional heterogeneity in D2 and D3 expression. Also, the BPND in the striatal and its closely neighbor regions such as the ventral striatum and globus pallidus could not be quantified using 11C-FLB 457 because a long time more than a few hours is needed for reaching equilibration in the striatum. Based on the distribution of D2 and D3 receptors and the technical matters as described above, we investigated the binding sites of pramipexole especially in the limbic system, thalamus and cortical regions. To our knowledge, this is the first in vivo study that has investigated the relationship between a dopamine agonist and its binding sites in extrastriatal regions. This study showed that a single dose of pramipexole 0.25 mg decreased BPND_Logan significantly in the prefrontal cortex, amygdala, and thalamus. The mesolimbic pathway begins in the ventral tegmental area of the midbrain and projects to the limbic areas, including the nucleus accumbens in the ventral striatum, amygdala, and hippocampus; it also projects to the cortical areas, including the prefrontal and Torin 1 cingulate cortices. The latter cortical pathway is called as the mesocortical pathway. Both pathways are known to be involved in the depressive state.