title: Dopamine D(2)/D(3) receptor binding of [(123)I]epidepride in risperidone-treatment chronic MK-801-induced rat schizophrenia model using nanoSPECT/CT neuroimaging.
abstract: BACKGROUND
  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 [(123)I]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., 0.3 mg/kg/day) or saline for 4 weeks. After 1-week administration of MK-801, rats in MK-801+risperidone group received risperidone (0.5 mg/kg/day) intraperitoneally 15 min prior to MK-801 administration for the rest of 3-week treatment. We obtained serial [(123)I]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, [(123)I]epidepride nanoSPECT/CT neuroimaging revealed that low specific [(123)I]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 4 weeks. [(123)I]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, [(123)I]epidepride can be a useful tool to evaluate therapeutic effects of antipsychotic drug in chronic MK-801-induced rat schizophrenia model.
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan 325, Taiwan. Electronic address: yuanruei@iner.gov.tw.
authors.forename: Y R
authors.initials: YR
authors.lastname: Huang
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan 325, Taiwan.
authors.forename: C W
authors.initials: CW
authors.lastname: Pai
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan 325, Taiwan.
authors.forename: K H
authors.initials: KH
authors.lastname: Cheng
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan 325, Taiwan.
authors.forename: W I
authors.initials: WI
authors.lastname: Kuo
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan 325, Taiwan.
authors.forename: M W
authors.initials: MW
authors.lastname: Chen
authors.affiliation: Institute of Nuclear Energy Research, Taoyuan 325, Taiwan.
authors.forename: K W
authors.initials: KW
authors.lastname: Chang
mesh_terms: D000818:Animals; D001549:Benzamides / Q000378:metabolism*; D002908:Chronic Disease; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000009:adverse effects*; D008297:Male; D064847:Multimodal Imaging; D059906:Neuroimaging; D011485:Protein Binding; D011759:Pyrrolidines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D018967:Risperidone / Q000494:pharmacology* / Q000627:therapeutic use; D012559:Schizophrenia / Q000139:chemically induced / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001549:Benzamides; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C063525:epidepride; D016291:Dizocilpine Maleate; D014446:Tyrosine 3-Monooxygenase; D018967:Risperidone
keywords: Dopamine D(2)/D(3) receptor; Epidepride; MK-801; Rat model; Risperidone; Schizophrenia