[123I]Epidepride neuroimaging of dopamine D2/D3 receptor in chronic MK-801-induced rat schizophrenia model

Purpose: [I-123]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 noncompetitive NMDA receptor antagonist, MK-801, to examine if [I-123]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, 0.3 mg/kg) or saline for 1 month. Afterwards, total distance traveled (cm) and social interaction changes were recorded. Radiochemical purity of [I-123]epidepride was analyzed by Radio-Thin-Layer Chromatography (chloroform: methanol, 9:1, v/v) and [I-123]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 [I-123]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, [I-123]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 [I-123]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. (C) 2012 Elsevier Inc. All rights reserved.