This article is a US government work and, as such, is in the public domain in the United States of America.
Occupancy of dopamine D2/3 receptors in rat brain by endogenous dopamine measured with the agonist positron emission tomography radioligand [11C]MNPA†
Article first published online: 23 JUL 2008
Published 2008 Wiley-Liss, Inc.
Volume 62, Issue 10, pages 756–763, October 2008
How to Cite
Seneca, N., Zoghbi, S. S., Skinbjerg, M., Liow, J.-S., Hong, J., Sibley, D. R., Pike, V. W., Halldin, C. and Innis, R. B. (2008), Occupancy of dopamine D2/3 receptors in rat brain by endogenous dopamine measured with the agonist positron emission tomography radioligand [11C]MNPA. Synapse, 62: 756–763. doi: 10.1002/syn.20549
- Issue published online: 25 JUL 2008
- Article first published online: 23 JUL 2008
- Manuscript Accepted: 28 MAR 2008
- Manuscript Received: 16 JAN 2008
- Intramural Program of the National Institute of Mental Health. Grant Number: Z01-MH-002795-06
- dopamine depletion;
- D2/3 receptor;
Estimates of dopamine D2/3 receptor occupancy by endogenous dopamine using positron emission tomography (PET) in animals have varied almost threefold. This variability may have been caused by incomplete depletion of dopamine or by the use of antagonist radioligands, which appear less sensitive than agonist radioligands to changes in endogenous dopamine. PET scans were performed in rats with the agonist PET radioligand [11C]MNPA ([O-methyl-11C]2-methoxy-N-propylnorapomorphine). [11C]MNPA was injected as a bolus plus constant infusion to achieve steady-state concentration in the body and equilibrium receptor binding in the brain. Radioligand binding was compared at baseline and after treatment with reserpine plus α-methyl-para-tyrosine, which cause ∼95% depletion of endogenous dopamine. Depletion of dopamine increased radioligand binding in striatum but had little effect in cerebellum. Striatal [11C]MNPA binding potential was 0.93 ± 0.12 at baseline and increased to 1.99 ± 0.25 after dopamine depletion. Occupancy of D2/3 receptors by endogenous dopamine at baseline was calculated to be ∼53%. Striatal binding was displaceable with raclopride, but not with BP 897 (a selective D3 compound), thus confirming the D2 receptor specificity of [11C]MNPA binding. Radioactivity extracted from rat brain contained only 8–10% radiometabolites and was insignificantly altered by administration of reserpine plus α-methyl-para-tyrosine. Hence, dopamine depletion did not increase the PET measurements via an effect on radiotracer metabolism. Our in vivo estimate of dopamine's occupancy of D2/3 receptors at baseline is higher than that previously reported using antagonist radioligands and PET, but is similar to that reported using agonist radioligands and ex vivo measurements. Synapse 62:756–763, 2008. Published 2008 Wiley-Liss, Inc.