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- Title
Dopamine Receptor-Mediated Regulation of Striatal CholinergicActivity<SBT>Positron Emission Tomography Studies withNorchloro[[sup 18]F]fluoroepibatidine</SBT>.
- Authors
Ding, Yu-Shin; Logan, Jean; Bermel, Rob; Garza, Victor; Rice, Onarae; Fowler, Joanna S.; Volkow, Nora D.
- Abstract
Abstract: Large numbers of in vitro studies and microdialysis studies suggest that dopaminergic regulation of striatal acetylcholine (ACh) output is via inhibitory dopamine D[sub 2] receptors and stimulatory dopamine D[sub 1] receptors. Questions remain as to the relative predominance of dopamine D[sub 2] versus D[sub 1] receptor modulation of striatal ACh output under physiological conditions. Using positron emission tomography, we first demonstrate that norchloro[[sup 18]F]fluoroepibatidine ([[sup 18]SF]NFEP), a selective nicotinic ACh receptor (nAChR) ligand, was sensitive to changes of striatal ACh concentration. We then examined the effect of quinpirole (D[sub 2] agonist), raclopride (D[sub 2] antagonist), SKF38393 (D[sub 1] agonist), and SCH23390 (D[sub 1] antagonist) on striatal binding of [[sup 18]F]NFEP in the baboon. Pretreatment with quinpirole increased the striatum (ST) to cerebellum (CB) ratio by 26 +/- 6%, whereas pretreatment with raclopride decreased the ST/CB ratio by 22 +/- 2%. The ratio of the distribution volume of [18F]NFEP in striatum to that in cerebellum, which corresponds to (B[sub max]/K[sub D]) + 1 (index for nAChR availability), also showed a significant increase (29 and 20%; n = 2) and decrease (20 +/- 3%; n = 3) after pretreatment with quinpirole and raclopride, respectively. However, both the D[sub 1] agonist and antagonist had no significant effect. This suggests that under physiological conditions the predominant influence of endogenous dopamine on striatal ACh output is dopamine D[sub 2], not D[sub 1], receptor-mediated. Key...
- Subjects
DOPAMINE; NICOTINIC receptors; ACETYLCHOLINE; BIOCHEMICAL mechanism of action
- Publication
Journal of Neurochemistry, 2000, Vol 74, Issue 4, p1514
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2000.0741514.x