Effect of reserpine-induced depletion of synaptic dopamine on [11C]raclopride binding to D2-dopamine receptors in the monkey brain

Synapse. 1997 Apr;25(4):321-5. doi: 10.1002/(SICI)1098-2396(199704)25:4<321::AID-SYN2>3.0.CO;2-C.

Abstract

Positron emission tomography was used to examine the in vivo binding of [11C]raclopride to D2-dopamine (DA) receptors in the striatum of two Cynomolgus monkeys after a single dose of reserpine (1 mg/kg, i.v.). A Scatchard procedure was repeated five times to follow D2 receptor density and apparent affinity for 7 weeks after reserpine. Reserpine-induced depletion of DA lead to a marked increase in [11C]raclopride binding, which was still detectable 20 days after treatment. Scatchard analyses indicated that the measured increase in [11C]raclopride binding reflected an increase in receptor affinity but no evident change in receptor density (Bmax). Thus, the increase in [11C]raclopride binding after reserpine should correspond to a reduced competition with endogenous DA for binding to D2 receptors. The results were used to estimate the DA-induced D2 occupancy to be about 40% at physiological conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Carbon Radioisotopes
  • Dopamine / metabolism*
  • Dopamine Antagonists / metabolism*
  • Kinetics
  • Macaca fascicularis
  • Male
  • Models, Theoretical
  • Raclopride
  • Radioligand Assay
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / metabolism*
  • Reserpine / pharmacology*
  • Salicylamides / metabolism*
  • Salicylamides / pharmacokinetics
  • Synapses / drug effects
  • Synapses / metabolism*
  • Tomography, Emission-Computed

Substances

  • Carbon Radioisotopes
  • Dopamine Antagonists
  • Receptors, Dopamine D2
  • Salicylamides
  • Raclopride
  • Reserpine
  • Dopamine