Long-term dopamine (DA) replacement therapy in Parkinson’s disease (PD) often leads to development of abnormal motor response and dyskinesia (Olanow et al., 2004) through poorly understood mechanisms. DA modulates the basal ganglia output through opposite effects on the postsynaptic DA receptors: D1 facilitation and D2-like (D2 and D3) inhibition (Beaulieu et al., 2005). Anatomically, D1 and D2-like receptors are partially segre- gated into the striatonigral (“direct”) and striatopallidal (“indirect”) projections or pathways (Gerfen et al., 1990). However, there is evidence of substantial co-localization of functional D1- and D2-like receptors on striatal medium spiny projection neurons (Aizman et al., 2000; Pollack, 2004) implying that cross-talk may occur both at circuitry and intracellular levels. DA receptors are 7 transmembrane G-protein-coupled receptors: D1 receptors are coupled to G αs/olf, increase cAMP levels and phosphorylation of DARPP-32 and proteins downstream (Bonci and Hopf, 2005). D2 are linked to Gαi, inhibit adenyl cyclases and activate G-protein-coupled inward-rectifying potassium channels (Girk) and phosphatases (Bonci and Hopf, 2005). D3 have no net effect on cAMP levels and may couple to both Gs and i proteins (Ilani et al., 2002). Notably, D1 and D2/D3 agonists induce opposite hemodynamic changes in the striatum measured by functional pharmacologic (ph)MRI; D1 agonists increase relative cerebral blood volume (rCBV) while D2 and D3 agonists decrease it (Chen et al., 2005; Choi et al., 2006). Pramipexole, a D3-preferring agonist, has been shown to reduce cerebral blood flow in cingulate and orbitofrontal areas in monkeys in a PET study (Black et al., 2002). These opposite effects correlate well with the D1-mediated facilitation and D2 gating roles on glutamate transmission in the striatum. While D3 receptors are not highly expressed in the motor regions of the striatum (Murray et al., 1994; Sokoloff et al., 1990), there is compelling evidence from postmortem studies, of L-DOPA induction of ectopic D3 receptor expression in D1-expressing medium spiny neurons in the striatum of parkinsonian rats (Bordet et al., 1997; Bordet et al., 2000) and macaques (Bezard et al., 2003; Quik et al., 2000). Furthermore, both the presence of L-DOPA-induced dyskinesias in primates (Bezard et al., 2003) and sensitization to L-DOPA in rats (Bordet et al., 1997; Bordet et al., 2000; Guillin et al., 2003) have been correlated with changes in D3 receptor expression in postmortem analyses. In this study we examined in vivo hemodynamic changes in response to D3 activation using ph MRI and (7-hydroxy-N,N-di-n-propyl-2 aminotetralin) 7-OHDPAT, in naive, parkinsonian and L-DOPA-treated rats and primates. 7-OHDPAT has a 10-fold higher affinity for the D3 (Missale et al., 1998; Sokoloff et al., 1990) compared to the D2 receptor.