Dopamine D2/D3 receptor binding of [123I]epidepride in risperidone-treatment chronic MK-801-induced rat schizophrenia model using nanoSPECT/CT neuroimaging

Y. R. Huang, C. W. Pai, K. H. Cheng, W. I. Kuo, M. W. Chen, K. W. Chang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Introduction: Epidepride is a compound with an affinity in picomolar range for D2/D3 receptors. The aim of this work was designed to investigate the diagnostic possibility of [123I]epidepride imaging platform for risperidone-treatment chronic MK-801-induced rat schizophrenia model. Methods: Rats received repeated administration of MK-801 (dissolved in saline, i.p., 0.3mg/kg/day) or saline for 4weeks. After 1-week administration of MK-801, rats in MK-801+risperidone group received risperidone (0.5mg/kg/day) intraperitoneally 15min prior to MK-801 administration for the rest of 3-week treatment. We obtained serial [123I]epidepride neuroimages from nanoSPECT/CT and evaluated the alteration of specific binding in striatum and midbrain. Results: Risperidone reversed chronic MK-801-induced decrease in social interaction duration. IHC and ELISA analysis showed consistent results that chronic MK-801 treatment significantly decreased striatal and midbrain D2R expression but repeated risperidone administration reversed the effect of MK-801 treatment. In addition, [123I]epidepride nanoSPECT/CT neuroimaging revealed that low specific [123I]epidepride binding ratios caused by MK-801 in striatum and midbrain were statistically alleviated after 1- and 2-week risperidone administration, respectively. Conclusions: We established a rat schizophrenia model by chronic MK-801 administration for 4weeks. [123I]Epidepride nanoSPECT neuroimaging can trace the progressive alteration of D2R expression in striatum and midbrain caused by long-lasting MK-801 treatment. Besides diagnosing illness stage of disease, [123I]epidepride can be a useful tool to evaluate therapeutic effects of antipsychotic drug in chronic MK-801-induced rat schizophrenia model.

Original languageEnglish
Pages (from-to)681-687
Number of pages7
JournalNuclear Medicine and Biology
Volume41
Issue number8
DOIs
Publication statusPublished - Sep 2014
Externally publishedYes

Fingerprint

Dopamine D3 Receptors
Risperidone
Dizocilpine Maleate
Dopamine D2 Receptors
Neuroimaging
Schizophrenia
Mesencephalon
Therapeutics
epidepride
Corpus Striatum
Therapeutic Uses
Interpersonal Relations
Antipsychotic Agents

Keywords

  • Epidepride
  • MK-801
  • Rat model
  • Risperidone
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Dopamine D2/D3 receptor binding of [123I]epidepride in risperidone-treatment chronic MK-801-induced rat schizophrenia model using nanoSPECT/CT neuroimaging. / Huang, Y. R.; Pai, C. W.; Cheng, K. H.; Kuo, W. I.; Chen, M. W.; Chang, K. W.

In: Nuclear Medicine and Biology, Vol. 41, No. 8, 09.2014, p. 681-687.

Research output: Contribution to journalArticle

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abstract = "Introduction: Epidepride is a compound with an affinity in picomolar range for D2/D3 receptors. The aim of this work was designed to investigate the diagnostic possibility of [123I]epidepride imaging platform for risperidone-treatment chronic MK-801-induced rat schizophrenia model. Methods: Rats received repeated administration of MK-801 (dissolved in saline, i.p., 0.3mg/kg/day) or saline for 4weeks. After 1-week administration of MK-801, rats in MK-801+risperidone group received risperidone (0.5mg/kg/day) intraperitoneally 15min prior to MK-801 administration for the rest of 3-week treatment. We obtained serial [123I]epidepride neuroimages from nanoSPECT/CT and evaluated the alteration of specific binding in striatum and midbrain. Results: Risperidone reversed chronic MK-801-induced decrease in social interaction duration. IHC and ELISA analysis showed consistent results that chronic MK-801 treatment significantly decreased striatal and midbrain D2R expression but repeated risperidone administration reversed the effect of MK-801 treatment. In addition, [123I]epidepride nanoSPECT/CT neuroimaging revealed that low specific [123I]epidepride binding ratios caused by MK-801 in striatum and midbrain were statistically alleviated after 1- and 2-week risperidone administration, respectively. Conclusions: We established a rat schizophrenia model by chronic MK-801 administration for 4weeks. [123I]Epidepride nanoSPECT neuroimaging can trace the progressive alteration of D2R expression in striatum and midbrain caused by long-lasting MK-801 treatment. Besides diagnosing illness stage of disease, [123I]epidepride can be a useful tool to evaluate therapeutic effects of antipsychotic drug in chronic MK-801-induced rat schizophrenia model.",
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AB - Introduction: Epidepride is a compound with an affinity in picomolar range for D2/D3 receptors. The aim of this work was designed to investigate the diagnostic possibility of [123I]epidepride imaging platform for risperidone-treatment chronic MK-801-induced rat schizophrenia model. Methods: Rats received repeated administration of MK-801 (dissolved in saline, i.p., 0.3mg/kg/day) or saline for 4weeks. After 1-week administration of MK-801, rats in MK-801+risperidone group received risperidone (0.5mg/kg/day) intraperitoneally 15min prior to MK-801 administration for the rest of 3-week treatment. We obtained serial [123I]epidepride neuroimages from nanoSPECT/CT and evaluated the alteration of specific binding in striatum and midbrain. Results: Risperidone reversed chronic MK-801-induced decrease in social interaction duration. IHC and ELISA analysis showed consistent results that chronic MK-801 treatment significantly decreased striatal and midbrain D2R expression but repeated risperidone administration reversed the effect of MK-801 treatment. In addition, [123I]epidepride nanoSPECT/CT neuroimaging revealed that low specific [123I]epidepride binding ratios caused by MK-801 in striatum and midbrain were statistically alleviated after 1- and 2-week risperidone administration, respectively. Conclusions: We established a rat schizophrenia model by chronic MK-801 administration for 4weeks. [123I]Epidepride nanoSPECT neuroimaging can trace the progressive alteration of D2R expression in striatum and midbrain caused by long-lasting MK-801 treatment. Besides diagnosing illness stage of disease, [123I]epidepride can be a useful tool to evaluate therapeutic effects of antipsychotic drug in chronic MK-801-induced rat schizophrenia model.

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