Journal of Neural Transmission

, Volume 104, Issue 4, pp 329–339

Amphetamine effects on dopamine release and synthesis rate studied in the Rhesus monkey brain by positron emission tomography

  • P. Hartvig
  • R. Torstenson
  • J. Tedroff
  • Y. Watanabe
  • K. J. Fasth
  • P. Bjurling
  • B. Långström
Basic Neurosciences and Genetics

DOI: 10.1007/BF01277655

Cite this article as:
Hartvig, P., Torstenson, R., Tedroff, J. et al. J. Neural Transmission (1997) 104: 329. doi:10.1007/BF01277655

Summary

Positron emission tomography (PET) was used in a multitracer protocol to evaluate D-amphetamine induced effects on dopamine biosynthesis rate and release in propofol anesthetized Rhesus monkeys.l-[β-11C]DOPA was used as biochemical probe to study the brain dopamine biosynthesis rate whilst dopamine release was followed by the binding displacement of the [11C]-radiolabelled dopamine receptor antagonists, raclopride and N-methylspiperone. Studies were performed with either a constant rate intravenous infusion of D-amphetamine aiming at plasma concentrations of 0.2 to 25 ng/ml or with intravenous bolus doses of 0.1 and 0.4 mg/ kg. Decreased binding of the dopamine receptor antagonists was measured in both modes of D-amphetamine administration but notably [11C]N-methylspiperone was less able to sense D-amphetamine induced release of dopamine. At plasma concentrations aimed above 1 ng/ml a levelling off of the binding of [11C]raclopride at 68 ± 8.1% of the baseline value indicated that displacement was only possible from a fraction of the binding sites. Amphetamine was observed to increase the rate constant forl-[β-11C]DOPA utilization in the brain. This was most likely due to an acutely induced subsensitivity of presynaptic dopamine receptors.l-[β-11C]DOPA and [11C]raclopride were found suitable to indicate changes in dopamine synthesis rate and release respectively using PET and can be used to mirror drug-induced changes of brain dopaminergic function.

Keywords

Amphetamine[11C]L-DOPAracloprideN-methylspiperoneCBFPETmonkeys

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • P. Hartvig
    • 1
    • 2
    • 4
  • R. Torstenson
    • 1
    • 2
  • J. Tedroff
    • 1
    • 3
  • Y. Watanabe
    • 1
    • 4
  • K. J. Fasth
    • 1
    • 4
  • P. Bjurling
    • 1
    • 4
  • B. Långström
    • 1
    • 4
  1. 1.Uppsala University PET CentreUniversity Hospital, University of UppsalaUppsalaSweden
  2. 2.Hospital PharmacyUniversity Hospital, University of UppsalaUppsalaSweden
  3. 3.Department of NeurologyUniversity Hospital, University of UppsalaUppsalaSweden
  4. 4.Research and Development Corporation of JapanSubfemtomole Biorecognition ProjectJapan