title: [123I]Epidepride neuroimaging of dopamine D2/D3 receptor in chronic MK-801-induced rat schizophrenia model.
abstract: OBJECTIVE
  [(123)I]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 [(123)I]epidepride could be used to evaluate the alterations of dopamine D(2)/D(3) receptor binding condition in specific brain regions.
  
  
  METHODS
  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 [(123)I]epidepride was analyzed by Radio-Thin-Layer Chromatography (chloroform: methanol, 9:1, v/v) and [(123)I]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.
  
  
  RESULTS
  Chronic MK-801 treatment for a month caused significantly increased local motor activity and induced an inhibition of social interaction. As shown in [(123)I]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, [(123)I]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.
  
  
  CONCLUSIONS
  These results suggest that [(123)I]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.
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan 325, Taiwan, ROC. yuanruei@iner.gov.tw
authors.forename: Yuan-Ruei
authors.initials: YR
authors.lastname: Huang
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Shih
authors.forename: Kang-Wei
authors.initials: KW
authors.lastname: Chang
authors.forename: Chieh
authors.initials: C
authors.lastname: Huang
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Wu
authors.forename: Chia-Chieh
authors.initials: CC
authors.lastname: Chen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides; D002908:Chronic Disease; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D008297:Male; D064847:Multimodal Imaging; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D059906:Neuroimaging / Q000379:methods*; D049268:Positron-Emission Tomography; D011759:Pyrrolidines; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000032:analysis / Q000378:metabolism*; D012559:Schizophrenia / Q000139:chemically induced / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism*; D014057:Tomography, X-Ray Computed; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001549:Benzamides; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C063525:epidepride; D016291:Dizocilpine Maleate; D014446:Tyrosine 3-Monooxygenase