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In vivo vulnerability to competition by endogenous dopamine: Comparison of the D 2 receptor agonist radiotracer (–)‐N‐[ 11 C]propyl‐norapomorphine ([ 11 C]NPA) with the D 2 receptor antagonist radiotracer [ 11 C]‐raclopride
Author(s) -
Narendran Rajesh,
Hwang DahRen,
Slifstein Mark,
Talbot Peter S.,
Erritzoe David,
Huang Yiyun,
Cooper Thomas B.,
Martinez Diana,
Kegeles Lawrence S.,
AbiDargham Anissa,
Laruelle Marc
Publication year - 2004
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20013
Subject(s) - raclopride , agonist , chemistry , in vivo , antagonist , receptor , binding potential , amphetamine , endogenous agonist , pharmacology , dopamine , dopamine uptake inhibitors , sch 23390 , medicine , endocrinology , dopamine receptor d1 , biochemistry , biology , nucleus accumbens , microbiology and biotechnology
(–)‐N‐Propyl‐norapomorphine (NPA) is a full dopamine (DA) D 2 receptor agonist and [ 11 C]NPA is a suitable radiotracer to image D 2 receptors configured in a state of high affinity for agonists with positron emission tomography (PET). In this study the vulnerability of the in vivo binding of [ 11 C]NPA to acute fluctuation in synaptic DA was assessed with PET in baboons and compared to that of the reference D 2 receptor antagonist radiotracer [ 11 C]raclopride. Three male baboons were studied with [ 11 C]raclopride and [ 11 C]NPA under baseline conditions and following administration of the potent DA releaser amphetamine (0.3, 0.5, and 1.0 mg kg –1 i.v.). Kinetic modeling with an arterial input function was used to derive the striatal specific‐to‐nonspecific equilibrium partition coefficient (V 3 ″). [ 11 C]Raclopride V 3 ″ was reduced by 24 ± 10%, 32 ± 6%, and 44 ± 9% following amphetamine doses of 0.3, 0.5, and 1.0 mg kg –1 , respectively. [ 11 C]NPA V 3 ″ was reduced by 32 ± 2%, 45 ± 3%, and 53 ± 9% following amphetamine doses of 0.3, 0.5, and 1.0 mg kg –1 , respectively. Thus, endogenous DA was more effective at competing with [ 11 C]NPA binding compared to [ 11 C]raclopride binding, a finding consistent with the pharmacology of these tracers (agonist vs. antagonist). These results also suggest that 71% of D 2 receptors are configured in a state of high affinity for agonists in vivo. In conclusion, [ 11 C]NPA might provide a superior radiotracer to probe presynaptic DA function with PET in health and disease. Synapse 52:188–208, 2004. © 2004 Wiley‐Liss, Inc.