Sensitivity of striatal [11C]cocaine binding to decreases in synaptic dopamine.
We have previously shown that tracer concentrations of [11C]cocaine binding to the dopamine transporter (DAT) in human and baboon striatum can be visualized using positron emission tomography (PET). To determine whether the concentration of dopamine normally present in the synaptic cleft can compete with [11C]cocaine for transporter binding sites, we conducted baboon PET studies with drugs (sodium 4-hydroxybutyrate, four studies, 200 mg/kg; gamma-vinylGABA, three studies, 300 mg/kg; and citalopram, three studies, 2 mg/kg) expected to decrease synaptic dopamine. Each study involved two [11C]cocaine injections and PET scans separated by 2-4 h, with drug administration after the first injection, and without movement of the subject between scans. Time-activity data from striatum and from cerebellum were used with the arterial plasma input function to determine graphically by Logan plotting [11C]cocaine distribution volumes for the brain regions. Specific binding of [11C]cocaine to DAT in striatum was calculated as the distribution volume ratio (DVR) for striatum and cerebellum. In nine of the ten studies drug treatment produced a small increase in DVR (range, 1-11%), and in seven of these studies the increase was > or = 7%. The mean increase was 6.2 +/- 4.1%. The reproducibility of the DVR measure was assessed by comparing [11C]cocaine studies conducted without pharmacological treatments using individual baboons on separate days, and thus involving possible repositioning errors, as well as long-term changes in the state of the striatal dopamine system.(ABSTRACT TRUNCATED AT 250 WORDS)
Gatley
S J
SJ
Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
Volkow
N D
ND
Fowler
J S
JS
Dewey
S L
SL
Logan
J
J
D000818:Animals; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism*; D015283:Citalopram / Q000378:metabolism; D003042:Cocaine / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010215:Papio; D017729:Presynaptic Terminals / Q000000981:diagnostic imaging / Q000378:metabolism*; D013997:Time Factors; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015283:Citalopram; D003042:Cocaine; D004298:Dopamine