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

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. 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. 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. 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.