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Dopamine Receptor‐Mediated Regulation of Striatal Cholinergic Activity
Author(s) -
Ding YuShin,
Logan Jean,
Bermel Rob,
Garza Victor,
Rice Onarae,
Fowler Joanna S.,
Volkow Nora D.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741514.x
Subject(s) - raclopride , quinpirole , agonist , medicine , dopaminergic , endocrinology , chemistry , dopamine , striatum , dopamine receptor d1 , dopamine receptor d2 , receptor , biology
Large numbers of in vitro studies and microdialysisstudies suggest that dopaminergic regulation of striatal acetylcholine (ACh)output is via inhibitory dopamine D 2 receptors and stimulatorydopamine D 1 receptors. Questions remain as to the relativepredominance of dopamine D 2 versus D 1 receptormodulation of striatal ACh output under physiological conditions.Using positron emission tomography, we first demonstrate thatnorchloro[ 18 F]fluoroepibatidine ([ 18 F]NFEP), a selectivenicotinic ACh receptor (nAChR) ligand, was sensitive to changes of striatalACh concentration. We then examined the effect of quinpirole (D 2 agonist), raclopride (D 2 antagonist), SKF38393 (D 1 agonist), and SCH23390 (D 1 antagonist) on striatal binding of[ 18 F]NFEP in the baboon. Pretreatment with quinpirole increased thestriatum (ST) to cerebellum (CB) ratio by 26 ± 6%, whereas pretreatmentwith raclopride decreased the ST/CB ratio by 22 ± 2%. The ratio of thedistribution volume of [ 18 F]NFEP in striatum to that in cerebellum,which corresponds to ( B max / K D ) + 1(index for nAChR availability), also showed a significant increase (29 and20%; n = 2) and decrease (20 ± 3%; n = 3) after pretreatment withquinpirole and raclopride, respectively. However, both the D 1 agonist and antagonist had no significant effect. This suggests that under physiological conditions the predominant influence of endogenousdopamine on striatal ACh output is dopamine D 2 , not D 1 , receptor‐mediated.