The time course of the loss in presynaptic dopamine transporters (DAT) and of the increase in postsynaptic dopamine D2 receptors (D2R) was studied in a rat model of Parkinson's disease. For this, in vitro autoradiographic experiments were performed in the striatum using (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-methy lphenyl) nortropane (PE2I), a new single photon emission tomography (SPET) ligand for DAT, and iodobenzamide (IBZM), a SPET ligand for D2R. A significant decrease in [125I]PE2I binding was observed as early as 24 h after 6-hydroxydopamine lesion, whereas no change occurred in [125I]IBZM binding. At 48 h postlesion, PE2I binding was 50% decreased, while IBZM binding was 30% increased. Between 3 and 14 days postlesion, PE2I binding had almost totally disappeared and IBZM binding remained increased by around 40-50%. From these animal experiments, it can be assumed that PE2I would be very efficient for the detection of a reduction in the number of DAT reflecting neuronal loss, thus allowing early diagnosis of Parkinson's disease. The exploration of both DAT and D2R would improve follow-up of this disease.