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[123I]FP-CIT SPECT measurement of synaptic dopamine changes in rat brain following acute administration of antipsychotic drugs : [123I]FP-CIT SPECT를 이용한 항정신병약물에 의한 시냅스 도파민 변화의 평가

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융합과학기술대학원 융합과학부
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서울대학교 대학원
학위논문 (석사)-- 서울대학교 대학원 : 융합과학기술대학원 융합과학부, 2018. 8. 김상은.
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 is a technique that could allow the assessment of changes in synaptic DA concentration 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 midbrain and striatum of rats to assess the utility of [123I]FP-CIT SPECT for quantitating changes in synaptic DA concentrations. Rats were examined by [123I]FP-CIT SPECT after administration of conventional dose of HAL (1 mg/kg) and CLZ (10 mg/kg). Drugs were intraperitoneally injected 30 min before radiotracer injection. Regional brain changes (%) in [123I]FP-CIT non-displaceable binding potential (BPND) between drug treatment conditions were calculated by an equilibrium ratio method. In another experiment, changes in endogenous DA concentration in the striatum were monitored by in vivo microdialysis under the same conditions as in the SPECT study. Compared to normal saline, HAL treatment decreased [123I]FP-CIT BPND in the midbrain (−58.74% for 1 mg/kg) and striatum (−25.29% for 1 mg/kg), whereas in the CLZ-treated group, [123I]FP-CIT BPND was decreased in the midbrain (−38.60% for 10 mg/kg) but was 18.85% increased in the striatum. Changes in extracellular DA concentration induced by the different treatments varied according to the drug and across brain regions. [123I]FP-CIT SPECT is a useful preclinical technique for detecting apparent increases in DA concentration induced by acute HAL administration in both midbrain and striatum, with results comparable to those obtained by in vivo microdialysis.
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