Pretreatment with haloperidol reduces (123)I-FP-CIT binding to the dopamine transporter in the rat striatum: an in vivo imaging study with a dedicated small-animal SPECT camera.
Synaptic dopamine is mainly regulated by presynaptic dopamine transporter (DAT) activity. We hypothesized that variations in synaptic dopamine are reflected by variations of DAT radioligand binding. The effect of haloperidol, which increases synaptic dopamine concentrations, was therefore assessed in the rat striatum using (123)I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)-nortropane ((123)I-FP-CIT) as a DAT radioligand.


METHODS
Striatal (123)I-FP-CIT binding was measured in 24 rats under baseline conditions (no pretreatment) and at 1 h after injection of haloperidol or a vehicle (1 mg/kg) using a small-animal SPECT camera.


RESULTS
Baseline equilibrium ratios (V(3)'') were 1.32 +/- 0.24 (mean +/- SD). After the haloperidol injection, V(3)'' decreased to 0.99 +/- 0.38 (P(2-tailed) < 0.0001), corresponding to a mean reduction of DAT binding by 25%.


CONCLUSIONS
Our results are indicative of competition between the DAT ligand (123)I-FP-CIT and synaptic dopamine elevated by haloperidol, suggesting that the assessment of (123)I-FP-CIT binding may be suitable to study variations in synaptic dopamine in vivo.
Nikolaus
Susanne
S
Clinic of Nuclear Medicine, University Hospital Düsseldorf, Düsseldorf, Germany. Susanne.Nikolaus@uni-duesseldorf.de
Antke
Christina
C
Kley
Konstantin
K
Beu
Markus
M
Wirrwar
Andreas
A
Müller
Hans-Wilhelm
HW
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000008:administration & dosage*; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000187:drug effects; D015899:Tomography, Emission-Computed, Single-Photon / Q000295:instrumentation / Q000379:methods* / Q000662:veterinary; D014326:Tropanes / Q000493:pharmacokinetics*
D014150:Antipsychotic Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D006220:Haloperidol