Pretreatment with haloperidol reduces 123I-FP-CIT binding to the dopamine transporter in the rat striatum: An in vivo imaging study with a dedicated small-animal SPECT camera

Abstract

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 123I-N-ω-fluoropropyl-2β-carbomethoxy- 3β-(4-iodophenyl)-nortropane (123I-FP-CIT) as a DAT radioligand. Methods: Striatal 123I-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 (V3″) were 1.32 ± 0.24 (mean ± SD). After the haloperidol injection, V3″ decreased to 0.99 ± 0.38 (P2-tailed < 0.0001), corresponding to a mean reduction of DAT binding by 25%. Conclusion: Our results are indicative of competition between the DAT ligand 123I-FP-CIT and synaptic dopamine elevated by haloperidol, suggesting that the assessment of 123I-FP- CIT binding may be suitable to study variations in synaptic dopamine in vivo. Copyright © 2009 by the Society of Nuclear Medicine, Inc.