[ 123I]Epidepride neuroimaging of dopamine D 2/D 3 receptor in chronic MK-801-induced rat schizophrenia model

Yuan Ruei Huang, Jun Ming Shih, Kang Wei Chang, Chieh Huang, Yu Lung Wu, Chia Chieh Chen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: [ 123I]Epidepride is a radio-tracer with very high affinity for dopamine D 2/D 3 receptors in brain. The importance of alteration in dopamine D 2/D 3 receptor binding condition has been wildly verified in schizophrenia. In the present study we set up a rat schizophrenia model by chronic injection of a non-competitive NMDA receptor antagonist, MK-801, to examine if [ 123I]epidepride could be used to evaluate the alterations of dopamine D 2/D 3 receptor binding condition in specific brain regions. Method: Rats were given repeated injection of MK-801 (dissolved in saline, 0.3mg/kg) or saline for 1month. Afterwards, total distance traveled (cm) and social interaction changes were recorded. Radiochemical purity of [ 123I]epidepride was analyzed by Radio-Thin-Layer Chromatography (chloroform: methanol, 9:1, v/v) and [ 123I]epidepride neuroimages were obtained by ex vivo autoradiography and small animal SPECT/CT. Data obtained were then analyzed to determine the changes of specific binding ratio. Result: Chronic MK-801 treatment for a month caused significantly increased local motor activity and induced an inhibition of social interaction. As shown in [ 123I]epidepride ex vivo autoradiographs, MK-801 induced a decrease of specific binding ratio in the striatum (24.01%), hypothalamus (35.43%), midbrain (41.73%) and substantia nigra (37.93%). In addition, [ 123I]epidepride small animal SPECT/CT neuroimaging was performed in the striatum and midbrain. There were statistically significant decreases in specific binding ratio in both the striatum (P<.01) and midbrain (P<.05) between the saline and MK-801 group. Conclusion: These results suggest that [ 123I]epidepride is a useful radio-tracer to reveal the alterations of dopamine D 2/D 3 receptor binding in a rat schizophrenia model and is also helpful to evaluate therapeutic effects of schizophrenia in the future.

Original languageEnglish
Pages (from-to)826-832
Number of pages7
JournalNuclear Medicine and Biology
Volume39
Issue number6
DOIs
Publication statusPublished - Aug 1 2012
Externally publishedYes

Fingerprint

Dizocilpine Maleate
Neuroimaging
Dopamine
Schizophrenia
Mesencephalon
Radio
Interpersonal Relations
Injections
Brain
Therapeutic Uses
Substantia Nigra
Thin Layer Chromatography
Chloroform
epidepride
N-Methyl-D-Aspartate Receptors
Autoradiography
Hypothalamus
Methanol
Motor Activity

Keywords

  • Dopamine D /D receptor
  • Epidepride
  • Midbrain
  • MK-801
  • Schizophrenia
  • Striatum

ASJC Scopus subject areas

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

Cite this

[ 123I]Epidepride neuroimaging of dopamine D 2/D 3 receptor in chronic MK-801-induced rat schizophrenia model. / Huang, Yuan Ruei; Shih, Jun Ming; Chang, Kang Wei; Huang, Chieh; Wu, Yu Lung; Chen, Chia Chieh.

In: Nuclear Medicine and Biology, Vol. 39, No. 6, 01.08.2012, p. 826-832.

Research output: Contribution to journalArticle

Huang, Yuan Ruei ; Shih, Jun Ming ; Chang, Kang Wei ; Huang, Chieh ; Wu, Yu Lung ; Chen, Chia Chieh. / [ 123I]Epidepride neuroimaging of dopamine D 2/D 3 receptor in chronic MK-801-induced rat schizophrenia model. In: Nuclear Medicine and Biology. 2012 ; Vol. 39, No. 6. pp. 826-832.
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abstract = "Purpose: [ 123I]Epidepride is a radio-tracer with very high affinity for dopamine D 2/D 3 receptors in brain. The importance of alteration in dopamine D 2/D 3 receptor binding condition has been wildly verified in schizophrenia. In the present study we set up a rat schizophrenia model by chronic injection of a non-competitive NMDA receptor antagonist, MK-801, to examine if [ 123I]epidepride could be used to evaluate the alterations of dopamine D 2/D 3 receptor binding condition in specific brain regions. Method: Rats were given repeated injection of MK-801 (dissolved in saline, 0.3mg/kg) or saline for 1month. Afterwards, total distance traveled (cm) and social interaction changes were recorded. Radiochemical purity of [ 123I]epidepride was analyzed by Radio-Thin-Layer Chromatography (chloroform: methanol, 9:1, v/v) and [ 123I]epidepride neuroimages were obtained by ex vivo autoradiography and small animal SPECT/CT. Data obtained were then analyzed to determine the changes of specific binding ratio. Result: Chronic MK-801 treatment for a month caused significantly increased local motor activity and induced an inhibition of social interaction. As shown in [ 123I]epidepride ex vivo autoradiographs, MK-801 induced a decrease of specific binding ratio in the striatum (24.01{\%}), hypothalamus (35.43{\%}), midbrain (41.73{\%}) and substantia nigra (37.93{\%}). In addition, [ 123I]epidepride small animal SPECT/CT neuroimaging was performed in the striatum and midbrain. There were statistically significant decreases in specific binding ratio in both the striatum (P<.01) and midbrain (P<.05) between the saline and MK-801 group. Conclusion: These results suggest that [ 123I]epidepride is a useful radio-tracer to reveal the alterations of dopamine D 2/D 3 receptor binding in a rat schizophrenia model and is also helpful to evaluate therapeutic effects of schizophrenia in the future.",
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