In vivo measures of dopaminergic radioligands in the rat brain: Equilibrium infusion studies
- 14 December 2001
- Vol. 43 (3) , 188-194
- https://doi.org/10.1002/syn.10039
Abstract
The application of an equilibrium infusion method for measuring specific in vivo radioligand binding in the conscious rat brain was evaluated for two ligands of the dopaminergic system, (+)-α-[11C]dihydrotetrabenazine (DTBZ) and d-threo-[11C]methylphenidate (MePhen). Both radioligands can be successfully utilized to reach equilibrium distributions in rat brain within 1 h; combinations of tritiated and carbon-11-labeled radiotracers can furthermore be used to obtain simultaneous measures of the neuronal membrane dopamine transporter (using [3H]MePhen) and vesicular monoamine transporter (using [11C]DTBZ) in the same animal. These studies provided quantitative measures of distribution volume ratios, which represent specific radioligand binding. Stereospecificity of in vivo binding was demonstrated using equilibrium infusions of the low-affinity isomers of each ligand, (−)-α-[11C]dihydrotetrabenazine (DTBZ) and l-threo-[11C]methylphenidate, both of which produced uniform brain distributions and no specific binding. Specific binding of (+)-α-[11C]dihydrotetrabenazine was blocked by co-infusion of tetrabenazine, but was unaffected by administration of methylphenidate, haloperidol, or apomorphine. Specific binding of d-threo-[11C]methylphenidate, conversely, was blocked with unlabeled methylphenidate but not affected by tetrabenazine or the dopamine receptor ligands. Equilibrium measures of in vivo radioligand binding, as utilized in this study, offer a quantitative means to evaluate acute and chronic drug effects on in vivo radioligand binding in the rat brain. Synapse 43:188–194, 2002.Keywords
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