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We compared extracellular effects directly against synaptic changes. ECF DA was assessed by microdialysis in freely moving rodents and synaptic dopamine (DA) was measured using PET and [<jats:sup>11<\/jats:sup>C]\u2010raclopride displacement in rodents and baboons. Microdialysis data demonstrated that MP (5.0 mg\/kg, i.p.) increased ECF DA 360% \u00b1 31% in striatum, which was significantly less than that by AMP (2.5 mg\/kg, i.p.; 1398% \u00b1 272%). This fourfold difference was not reflected by changes in synaptic DA. In fact, rodent PET studies showed no difference in striatal [<jats:sup>11<\/jats:sup>C]\u2010raclopride binding induced by AMP (2.5 mg\/kg, i.p.; 25% \u00b1 4% reduction) compared with that by MP (5.0 mg\/kg, i.p.; 21% \u00b1 4% reduction). Primate PET experiments also showed no differences between AMP (0.5 mg\/kg, i.v.; 24% \u00b1 4% reduction) and MP (1.0 mg\/kg, i.v.; 25% \u00b1 7% reduction) induced changes in [<jats:sup>11<\/jats:sup>C]\u2010raclopride binding potential. The similar potencies of MP and AMP to alter synaptic DA, despite their different potencies in raising ECF DA, could reflect their different molecular mechanisms. Synapse 59:243\u2013251, 2006. 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