Combined dopamine transporter and D2-receptor imaging in schizophrenia: Implications for atypical neuroleptics

Understanding the mode of pre- and postsynaptic regulation of striatal dopamine, especially the influence of neuroleptic therapy, seems to be one of the challenges of research in schizophrenia. Combineable radioligands of the pre- and post-synaptic side of the dopaminergic synapse are a new tool for getting deeper insight in the schizophrenic illness and effects of therapy in vivo. With a new SPECT-ligand to the presynaptic dopamine transporter (DAT), the 99mTc-labelled TRODAT-1, together with the well known postsynaptic D2-receptor ligand 123I-IBZM a technique for the simultaneous analysis pre- and postsynaptically of the striatal dopaminergic synapse is available now. Amisulpride acts antagonistically on pre- and postsynaptic D₂ and D₃ receptors with indication for a preferentially presynaptic binding in a low dosage range.

In our study we analyzed pre- and postsynaptic binding at the striatal dopaminergic synapse after a fourteen days steady state treatment of schizophrenic patients with amisulpride in a high (350–1200mg/day) and a low dose range (50–300mg/day). We compared D2-occupancy and DAT-occupancy between patients treated with amisulpride and haloperidole (4–20mg/day). We found a D2-occupancy of 76.4% in the whole amisulpride dose range, with 79.5% in the high dose and 72.7% in the low dose range. The haloperidol treated patients showed 85.7% D2-occupancy. DAT-occupancy with endogenous dopamine increased dose dependently, with a significant difference between the amisulpride low dose and the haloperidol treated patients. Additionally, even in the amisulpride high dose range with high D2-occupancy, patients produced less EPS than the haloperidol treated ones. Data are discussed with respect to binding theories of neuroleptics to the postsynaptic dopamine D2-receptor.