Dopamine depletion and in vivo binding of PET D1 receptor radioligands: implications for imaging studies in schizophrenia.
Recent positron emission tomography (PET) studies have assessed the level of dopamine (DA) D1 receptors in the prefrontal cortex (PFC) in patients with schizophrenia and have generated contradictory findings. In the PFC of patients with schizophrenia, the binding potential (BP) of [11C]NNC 112 has been reported as increased, while the BP of [11C]SCH 23390 was reported as decreased or unchanged. In this study, the effect of acute and subchronic DA depletion on the in vivo binding of [11C]NNC 112 and [3H]SCH 23390 was evaluated in rats. Acute DA depletion did not affect [11C]NNC 112 in vivo binding, but paradoxically decreased [3H]SCH 23390 in vivo binding. Subchronic DA depletion was associated with increased [11C]NNC 112 in vivo binding and decreased [3H]SCH 23390 in vivo binding. Together, these data demonstrate that the in vivo binding of these radiotracers is differentially affected by changes in endogenous DA tone, and suggest that alterations in the binding of these tracers in the PFC of patients with schizophrenia might reflect changes in D1 receptors secondary to sustained deficit in prefrontal DA function.
Guo
Ningning
N
Department of Psychiatry, Columbia University and New York State Psychiatric Institute, New York, NY 10032, USA. ng159@columbia.edu
Hwang
Dah-Ren
DR
Lo
Ee-Sing
ES
Huang
Yung-Yu
YY
Laruelle
Marc
M
Abi-Dargham
Anissa
A
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects; D000818:Animals; D001552:Benzazepines / Q000493:pharmacokinetics*; D001572:Benzofurans / Q000493:pharmacokinetics*; D001665:Binding Sites; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000009:adverse effects; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D012110:Reserpine / Q000009:adverse effects; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism*; D013997:Time Factors; D014316:Tritium; D019805:alpha-Methyltyrosine / Q000009:adverse effects
D018759:Adrenergic Uptake Inhibitors; D001552:Benzazepines; D001572:Benzofurans; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D017447:Receptors, Dopamine D1; D014316:Tritium; C077123:NNC 112; D019805:alpha-Methyltyrosine; D012110:Reserpine; D004298:Dopamine