Extrapyramidal side-effects and dopamine D_2/3 receptor binding in substantia nigra

Abstract

Background: The exact mechanisms for antipsychotic-induced extrapyramidal side-effects have remained obscure despite intensive research. Previous studies have highlighted a central role for nigral dopamine D₂ receptors in the control of motor functions. Aims: The aim of the present study was to examine relationships between dopamine D₂ receptor binding in both substantia nigra and temporal cortex with extrapyramidal symptoms among antipsychotic-treated patients with schizophrenia. Methods: Single-photon emission-computed tomography (SPECT) ligand [¹²³I]epidepride was used to determine dopamine D_2/3 apparent binding potential in 13 antipsychotic-treated (seven with clozapine, four with olanzapine and two with haloperidol) patients with schizophrenia. Extrapyramidal symptoms were assessed with the Simpson and Angus Scale (SAS). Results: A statistically significant correlation was observed between dopamine D_2/3 receptor apparent binding potential in the substantia nigra and extrapyramidal side-effects (r = −0.62, P = 0.024). No correlations were detected in the temporal cortex between dopamine D_2/3 receptor binding and extrapyramidal side-effects. Conclusions: These findings support the role of dopamine D₂ autoreceptors in substantia nigra regarding drug-induced movement disorders.

• Antipsychotics
• Dopamine
• Extrapyramidal symptoms
• Receptor binding
• Substantia nigra

Acknowledgements

The authors have no conflict of interest or financial involvement that might have biased the present work. This study was supported by the Research Council for Health of the Finnish Academy, an EVO grant from the Kuopio University Hospital, Annual EVO Financing from Niuvanniemi Hospital, and the Maire Taponen Foundation.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.