Dopamine modulating drugs influence striatal (+)‐[ 11 C]DTBZ binding in rats: VMAT2 binding is sensitive to changes in vesicular dopamine concentration

Binding of (+)‐[ 11 C]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 (+)‐[ 11 C]DTBZ is modestly increased in rat striatum following dopamine depletion with α‐methyl‐ p ‐tyrosine (α‐MPT, +14%) or d‐amphetamine (d‐AMPH, 20 mg/kg, +12%) and decreased following dopamine elevation with γ‐hydroxybutyrate (GHB, −16%) or levodopa (−20%). We suggest that in vivo (+)‐[ 11 C]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. Synapse 62:873–876, 2008. © 2008 Wiley‐Liss, Inc.