Dopamine modulating drugs influence striatal (+)-[11C]DTBZ binding in rats: VMAT2 binding is sensitive to changes in vesicular dopamine concentration.
Binding of (+)-[11C]DTBZ (dihydrotetrabenazine) to the striatal vesicular monoamine transporter (VMAT2) is widely considered to be a stable marker of dopamine neurone integrity. However, we now find that specific binding of a tracer dose of (+)-[11C]DTBZ is modestly increased in rat striatum following dopamine depletion with alpha-methyl-p-tyrosine (alpha-MPT, +14%) or d-amphetamine (d-AMPH, 20 mg/kg, +12%) and decreased following dopamine elevation with gamma-hydroxybutyrate (GHB, -16%) or levodopa (-20%). We suggest that in vivo (+)-[11C]DTBZ binding in imaging studies is subject to competition by vesicular dopamine and, in this respect, is not a "stable" dopamine biomarker as is generally assumed.
Tong
Junchao
J
Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. junchao_tong@camh.net
Wilson
Alan A
AA
Boileau
Isabelle
I
Houle
Sylvain
S
Kish
Stephen J
SJ
D000818:Animals; D002250:Carbon Radioisotopes / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
D002250:Carbon Radioisotopes; D015259:Dopamine Agents; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D004298:Dopamine; D013747:Tetrabenazine