Effect of acute antipsychotic administration on dopamine synthesis in rodents and human subjects using 6-[18F]-L-m-tyrosine.
Clinical effects of antipsychotic drugs are thought to be mediated primarily through antagonism of the dopamine D2 receptors. Recent studies have demonstrated increased aromatic decarboxylase activity following acute administration of dopamine D2 receptor antagonists both in vivo and ex vivo. However, this effect has never been demonstrated in human subjects. We studied the effect of acute antipsychotic administration on dopamine synthesis in rodents and healthy human subjects using 6-[18F]-L-m-tyrosine. In rats, we studied the effect of a single subcutaneous injection of haloperidol and risperidone on dopamine synthesis using 6-[18F]-L-m-tyrosine. In our human study, six healthy volunteers underwent two 6-[18F]-L-m-tyrosine PET scans, before and after 3 mg risperidone to measure the rate of accumulation of radioactivity in the striatum as an index of dopamine synthesis. The striatal/cerebellar radioactivity count ratio and the ratio of dopamine metabolites to dopamine concentration was significantly higher in all rodent treatment groups compared to controls. In the PET study we found no significant change in the rate of uptake in the striatum. Our results suggest that 6-[18F]-L-m-tyrosine PET may not be a useful tool in the study of the effect of antipsychotics on dopamine synthesis in human subjects.
Mamo
David
D
Department of Psychiatry, University of Toronto, Canada. david.mamo@camhpet.ca
Remington
Gary
G
Nobrega
Jose
J
Hussey
Doug
D
Chirakal
Raman
R
Wilson
Alan A
AA
Baker
Glen
G
Houle
Sylvain
S
Kapur
Shitij
S
D000328:Adult; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D004334:Drug Administration Schedule; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014055:Tomography, Emission-Computed / Q000379:methods; D014443:Tyrosine / Q000378:metabolism*
D014150:Antipsychotic Agents; D005462:Fluorine Radioisotopes; D014443:Tyrosine; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine