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Dopamine D2 High receptors measured ex vivo are elevated in amphetamine‐sensitized animals
Author(s) -
Seeman Philip
Publication year - 2009
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.20595
Subject(s) - raclopride , dopamine receptor d2 , dopamine , radioligand , agonist , chemistry , dopamine receptor d3 , dopamine receptor , receptor , amphetamine , medicine , endocrinology , endogenous agonist , pharmacology , dopamine receptor d1 , biology , biochemistry
Abstract Although dopamine supersensitivity is a fundamental aspect of diseases such as schizophrenia and Parkinson's disease, the molecular basis of dopamine supersensitivity is not known. Because behavioral dopamine supersensitivity is associated with a marked elevation of striatal dopamine D2 High receptors in vitro, it is important to develop methods to measure D2 High receptors in vivo. The present ex vivo study found that the dopamine agonist NPA ([‐]‐N‐propyl‐norapomorphine) inhibited the binding of the agonist [ 3 H](+)PHNO to rat striatal D2 receptors significantly more than the D2 antagonist [ 3 H]raclopride, when NPA was coinjected i.v. with each radioligand. These results suggest that the greater sensitivity of [ 3 H](+)PHNO to inhibition by the coinjected NPA reflects in vivo competition at D2 High receptors. Using rats that had been sensitized to amphetamine, this ex vivo method found that the specific binding of [ 3 H](+)PHNO that was displaced by 10 μg/kg of NPA was 2.4‐fold higher than that for control rats. These data agree with in vitro data showing a marked increase in D2 High sites after amphetamine sensitization. Therefore, it is recommended that this method of coinjecting the D2 radioligand and the dopamine agonist displacer be used in human positron tomography to detect D2 High receptors in health and disease. Synapse 63:186–192, 2009. © 2008 Wiley‐Liss, Inc.