Articles

Article

Original Article

Experimental Neurobiology 2019; 28(5): 602-611

Published online October 31, 2019

https://doi.org/10.5607/en.2019.28.5.602

© The Korean Society for Brain and Neural Sciences

Combination of In Vivo [123I]FP-CIT SPECT and Microdialysis Reveals an Antipsychotic Drug Haloperidol-induced Synaptic Dopamine Availability in the Rat Midbrain and Striatum

So Hyeon Park1, Yoo Sung Song2, Byung Seok Moon3, Byung Chul Lee2, Hyun Soo Park1,2* and Sang Eun Kim1,2,4*

1Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, 2Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul 03080, 3Department of Nuclear Medicine, Ewha Woman’s University Seoul Hospital, Ewha Womans University College of Medicine, Seoul 07804, 4Advanced Institutes of Convergence Technology, Suwon 16229, Korea

Correspondence to: Sang Eun Kim, TEL: 82-31-787-7671, FAX: 82-31-787-4018
e-mail: kse@snu.ac.kr
Hyun Soo Park, TEL: 82-31-787-2936, FAX: 82-31-787-4018
e-mail: hyuns@snu.ac.kr

Received: August 29, 2019; Revised: October 25, 2019; Accepted: October 29, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License
(http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Synaptic dopamine (DA) is mainly regulated by the presynaptic DA transporter (DAT). Single-photon emission computerized tomography (SPECT) with the DAT radiotracer [123I]FP-CIT assesses changes in synaptic DA availability when endogenous DA displaces [123I]FP-CIT or competes for DAT. Here, we investigated the effects of haloperidol (HAL) and clozapine (CLZ) on [123I]FP-CIT binding in the rat striatum and midbrain to assess the utility of [123I]FP-CIT SPECT to quantify changes in synaptic DA availability. Rats underwent [123I]FP-CIT SPECT after intraperitoneal administration of normal saline (vehicle), HAL (1 and 7 mg/kg), CLZ (10 and 54 mg/kg) and bupropion (BUP, a DAT blocker, 20 and 100 mg/kg). In the striatum and midbrain, percent differences in the nondisplaceable binding potential (BPND) of [123I]FP-CIT compared to the vehicle were calculated for the various drugs and doses. In another experiment, changes in endogenous striatal DA concentration were measured by in vivo microdialysis under the conditions used in the SPECT study. BUP dose-dependently occupied DAT at considerable levels. Compared to the vehicle, HAL decreased [123I]FP-CIT BPND in the striatum (−25.29% and −2.27% for 1 and 7 mg/kg, respectively) and to a greater degree in the midbrain (−58.74% and −49.64% for 1 and 7 mg/kg, respectively), whereas the CLZ-treated group showed a decrease in the midbrain (−38.60% and −40.38% for 10 and 54 mg/kg, respectively) but an increase in the striatum (18.85% and 38.64% for 10 and 54 mg/kg, respectively). Antipsychotic-induced changes in endogenous striatal DA concentrations varied across drugs and doses. The data demonstrate that [123I]FP-CIT SPECT may be a useful preclinical technique for detecting increases in synaptic DA availability in the midbrain and striatum in response to HAL, with results comparable to those of in vivo microdialysis.

Graphical Abstract


Keywords: [123I]FP-CIT SPECT, Dopamine availability, Haloperidol, Clozapine, In vivo microdialysis