Differential effects of scopolamine on in vivo binding of dopamine transporter and vesicular monoamine transporter radioligands in rat brain.
The in vivo equilibrium specific binding of d-threo-[3H]methylphenidate, a radioligand for the dopamine transporter (DAT), and +-alpha-[3H]dihydrotetrabenazine, a radioligand for the vesicular monoamine transporter (VMAT2), were examined in rat brain with and without prior administration of 5 mg/kg scopolamine. Drug-treated animals exhibited a 30% increase in d-threo-[3H]methylphenidate binding to the DAT in the striatum relative to controls. No changes in specific binding of +-alpha-[3H]dihydrotetrabenazine were observed in any brain region following scopolamine pretreatment. Cholinergic drugs thus differentially affect in vivo specific binding of DAT and VMAT2 radioligands, suggesting this should be a consideration in selection of in vivo markers for imaging studies of dopaminergic terminals in the brain of animals and humans.
Kilbourn
Michael R
MR
Department of Radiology, Division of Nuclear Medicine, University of Michigan Medical School, Ann Arbor 48109, USA. mkilbour@umich.edu
Kemmerer
Elyse S
ES
Desmond
Timothy J
TJ
Sherman
Philip S
PS
Frey
Kirk A
KA
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008774:Methylphenidate / Q000493:pharmacokinetics; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009479:Neuropeptides; D011869:Radioligand Assay; D051381:Rats; D012601:Scopolamine / Q000494:pharmacology*; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014316:Tritium; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D018727:Muscarinic Antagonists; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C493454:Slc18a2 protein, rat; C493216:Slc6a3 protein, rat; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D014316:Tritium; D008774:Methylphenidate; C032811:dihydrotetrabenazine; D012601:Scopolamine; D013747:Tetrabenazine