BioSpace Collaborative - Effects of Dopamine D2 Receptor Partial Agonist Antipsychotic Aripiprazole on Dopamine Synthesis in Human Brain Measured by PET with L-[ß-11C]DOPA

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Mental Health - Neuroscience - Radiology and Medical Imaging

Effects of Dopamine D2 Receptor Partial Agonist Antipsychotic Aripiprazole on Dopamine Synthesis in Human Brain Measured by PET with L-[ß-11C]DOPA
Published: Friday, September 28, 2012
Author: Hiroshi Ito et al.

by Hiroshi Ito, Harumasa Takano, Ryosuke Arakawa, Hidehiko Takahashi, Fumitoshi Kodaka, Keisuke Takahata, Tsuyoshi Nogami, Masayuki Suzuki, Tetsuya Suhara

Dopamine D₂ receptor partial agonist antipsychotic drugs can modulate dopaminergic neurotransmission as functional agonists or functional antagonists. The effects of antipsychotics on presynaptic dopaminergic functions, such as dopamine synthesis capacity, might also be related to their therapeutic efficacy. Positron emission tomography (PET) was used to examine the effects of the partial agonist antipsychotic drug aripiprazole on presynaptic dopamine synthesis in relation to dopamine D₂ receptor occupancy and the resulting changes in dopamine synthesis capacity in healthy men. On separate days, PET studies with [¹¹C]raclopride and L-[ß-¹¹C]DOPA were performed under resting condition and with single doses of aripiprazole given orally. Occupancy of dopamine D₂ receptors corresponded to the doses of aripiprazole, but the changes in dopamine synthesis capacity were not significant, nor was the relation between dopamine D₂ receptor occupancy and these changes. A significant negative correlation was observed between baseline dopamine synthesis capacity and changes in dopamine synthesis capacity by aripiprazole, indicating that this antipsychotic appears to stabilize dopamine synthesis capacity. The therapeutic effects of aripiprazole in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity. More...