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

Abstract

PURPOSE:

[(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.

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 [(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.

RESULT:

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.

CONCLUSION:

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: Yuan-Ruei Huang, Jun-Ming Shih, Kang-Wei Chang, Chieh Huang, Yu-Lung Wu, Chia-Chieh Chen
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 39 Issue 6 Pg. 826-32 (Aug 2012) ISSN: 1872-9614 [Electronic] United States
• PMID: 22464847 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Benzamides
• Iodine Radioisotopes
• Pyrrolidines
• Receptors, Dopamine D2
• Receptors, Dopamine D3
• epidepride
• Dizocilpine Maleate
• Tyrosine 3-Monooxygenase

Topics

• Animals
• Behavior, Animal (drug effects)
• Benzamides
• Chronic Disease
• Disease Models, Animal
• Dizocilpine Maleate (pharmacology)
• Iodine Radioisotopes
• Male
• Multimodal Imaging
• Neostriatum (diagnostic imaging, drug effects, metabolism)
• Neuroimaging (methods)
• Positron-Emission Tomography
• Pyrrolidines
• Rats
• Rats, Sprague-Dawley
• Receptors, Dopamine D2 (analysis, metabolism)
• Receptors, Dopamine D3 (analysis, metabolism)
• Schizophrenia (chemically induced, diagnosis, diagnostic imaging, metabolism)
• Tomography, X-Ray Computed
• Tyrosine 3-Monooxygenase (metabolism)