Journal of Neural Transmission

, Volume 104, Issue 4–5, 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

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-DOPA raclopride N-methylspiperone CBF PET monkeys 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andersson JLR (1995) A rapid and accurate method to realign PET scans utilizing image edge information. J Nucl Med 36: 657–669PubMedGoogle Scholar
  2. Argiolas A, Fadda F, Stefani E, Gessa GL (1978) Evidence for a direct action of amphetamine on dopamine metabolism in the rat substantia nigra in vivo. Naunyn Schmiedebergs Arch Pharmacol 301: 171–174PubMedGoogle Scholar
  3. Bjurling P, Watanabe Y, Oka S, Nagasawa T, Yamada H, Långström B (1990) Multienzymatic synthesis of 11C-labelled L-tyrosine and L-dopa. Acta Chem Scand 44: 178–182Google Scholar
  4. Brooks D, Ibanez V, Sawle GV (1992) Striatal D2 receptor status in patients with Parkinson's disease, striatonigral degeneration and progressive supranuclear palsy, measured with 11C-raclopride and positron emission tomography. Ann Neurol 31: 184–192PubMedGoogle Scholar
  5. Burt DR, Creese I, Snyder SS (1976) Properties of [3H]haloperidol and [3H]dopamine binding associated with dopamine receptors in calf brain membranes. Mol Pharmacol 12: 800–812PubMedGoogle Scholar
  6. Butcher SP, Fairbrother IS, Kelly JS, Arbuthnott GW (1988) Amphetamine-induced dopamine release in the rat striatum: an in vivo microdialys study. J Neurochem 50: 346–355PubMedGoogle Scholar
  7. Carson RE, Huang SC, Green MV (1986) Weighted integration method for local cerebral blood flow measurements with positron emission tomography. J Cereb Blood Flow Metab 6: 245–258PubMedGoogle Scholar
  8. Dewey SL, Logan J, Wolf AP, Brodie JD, Angrist B, Fowler JS (1991) Amphetamine induced decreases in (18F)-N-methylspiperidol binding in the baboon brain using positron emission tomography. Synapse 7: 324–327PubMedGoogle Scholar
  9. Dewey SL, Smith GS, Logan J, Brodie JD, Fowler JS, Wolf AP (1993) Striatal binding of the PET ligand11C-raclopride is altered by drugs that modify synaptic dopamine levels. Synapse 13: 350–356PubMedGoogle Scholar
  10. Dexamphetamine (1991) In: Dollery C et al. (eds) Therapeutic drugs, vol 1. Churchill Livingstone, Edinburgh, pp D50-D55Google Scholar
  11. Edling C, Hellman B, Arvidsson B, Lilja A, Andersson J, Hartvig P, Valind S, Långström B (1997) Positron emission tomography studies of subjects occupationally exposed organic solvents. Evidence of increased dopamine synthesis rate. Int Arch Occup Environ Health (in press)Google Scholar
  12. Eriksson L, Holte S, Bohm C, Kesselberg M. Hovander B (1988) Automated blood sampling systems for positron emission tomography. IEEE Trans Nucl Sci 35: 703–704Google Scholar
  13. Giros B, Jaber M, Jones SR, Wightmann RM, Caron MG (1996) Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379: 606–612PubMedGoogle Scholar
  14. Hartvig P, Ågren H, Reibring L, Tedroff J, Bjurling P, Kihlberg T, Långström B (1991) Brain kinetics of L-[β-11C]DOPA in humans studied by positron emission tomography. J Neural Transm [GenSect] 86: 25–41Google Scholar
  15. Hersovitch P, Markham J, Raichle ME (1983) Brain blood flow measured with intravenous H2 15O. I. Theory and error analysis. J Nucl Med 24: 782–789PubMedGoogle Scholar
  16. Innis RB, Malison RT, Al-Tikriti M, Hoffer PB, Sybirska EH, Scibyl JP, Zoghbi SS, Baldwin RM, Lamelle M, Smith EO, Charney DS, Heninger G, Elsworrth J, Roth RR (1992) Amphetamine-stimulated dopamine release competes in vivo for [123I]IBZM binding to the D2 receptor in nonhuman primates. Synapse 10: 177–184PubMedGoogle Scholar
  17. Kamata K, Rebec GV (1984) Long-term amphetamine treatment attenuates or reverses the depression of neuronal activity produced by dopamine agonists in the ventral tegmental area. Life Sci 34: 2419–2427PubMedGoogle Scholar
  18. Kuzcenski R, Segal D (1989) Concomitant characterization of behavioral and striatal neurotransmittor response to amphetamine using in vivo microdialysis. J Neurosci 9: 2051–2086PubMedGoogle Scholar
  19. Laruelle M, Iyer RN, Al-Tikritit MS, Zea-Ponce Y, Malison R, Zoghbi SS, Baldwin RM, Kung HF, Charney DS, Hoffer PB, Innis RB, Bradberry CW (1997) Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates. Synapse 25: 1–14PubMedGoogle Scholar
  20. Leshner AI (1996) Molecular mechanism of cocaine addiction. N Engl J Med 335: 128–129PubMedGoogle Scholar
  21. Lindner K-J, Hartvig P, Tedroff J, Ljungström A, Bjurling P, Långström B (1995) Liquid chromatography analysis of brain homogenates and microdialysates for the quantification ofl-[β-11C]DOPA and its metabolites for the validation of positron emission tomographic studies. J Pharm Biomed Anal 13(4–5): 361–367PubMedGoogle Scholar
  22. Logan J, Volkow ND, Fowler JS, Wang GJ, Dewey SL, Schlyer DJ, MacGregor RR (1993) The effects of change in blood flow on the distribution volume of (11C)raclopride binding. J Nucl Med 34: 200PGoogle Scholar
  23. Långström B, Antoni G, Halldin C, Gullberg P, Malmborg P, Någren K, Rimland A, Svärd H (1987) Synthesis of L- and D-(methyl11C)methionine. J Nucl Med 28: 1037–1040PubMedGoogle Scholar
  24. McMillen B (1983) CNS stimulants: two distinct mechanisms of action of amphetamine like drugs. Trends Pharmacol Sci Oct: 429–432Google Scholar
  25. Meyer E (1989) Simultaneous correction for tracer arrival delay and dispersion in CBF measurements by H2 15O autoradiographical method and dynamic PET. J Nucl Med 30: 1069–1078PubMedGoogle Scholar
  26. Miller HH, Shore P (1982) Effects of amphetamine and amfonelic acid on the disposition of striatal newly synthetized dopamine. Eur J Pharmacol 78: 33–44PubMedGoogle Scholar
  27. Raichle ME, Martin WR, Hersovitch P, Mintun MA, Markham J (1983) Brain blood flow measured with intravenous H2 15O. II. Implementation and validation. J Nucl Med 24: 790–798PubMedGoogle Scholar
  28. Seeman P, Guan HC, Niznik HB (1989) Endogenous dopamine lowers the dopamine D2 receptor density as measured by [3H]raclopride: implications for positron tomography of the human brain. Synapse 3: 96–96PubMedGoogle Scholar
  29. Seutin V, Verbanck P, Massotte L, Dresse A (1991) Acute amphetamine induced subsensitivity of A10 dopamine autoreceptors in vivo. Brain Res 558: 141–144PubMedGoogle Scholar
  30. Tedroff J, Aquilonius SM, Hartvig P, Bjurling P, Långström B (1992) Estimation of regional cerebral utilization of [11C]-1-3,4-dihydroxyphenylalanine (DOPA) in the primate by positron emission tomography. Acta Neurol Scand 85: 215–225Google Scholar
  31. Tedroff J, Pedersen M, Aquilonius SM, Hartvig P, Jacobson G, Långström B (1996) Levodopa-induced changes in synaptic dopamine in patients with Parkinson's disease as measured by [11C]raclopride displacement and PET. Neurology 46: 1430–1436PubMedGoogle Scholar
  32. Tedroff J, Torstenson R, Hartvig P, Lindner KJ, Watanabe Y, Bjurling P, Westerberg G, Långström B (1997) L-DOPA modulates striatal dopaminergic function in vivo: evidence from PET investigations in nonhuman primates. Synapse 25: 56–61PubMedGoogle Scholar
  33. Torstenson R, Hartvig P, Långström B, Tedroff J (1997) Differential effect of levodopa infusion in early and advanced Parkinson's disease. Ann Neurol (in press)Google Scholar
  34. White FJ, Wang RY (1984) Electrophysiological evidence for A10 dopamine autoreceptor subsensitivity following chronic D-amphetamine treatment. Brain Res 309: 283–292PubMedGoogle Scholar
  35. Young LT, Wong DF, Goldman S, Minkin E, Chen C, Matsumura K, Scheffel U, Wagner HN Jr (1991) Effects of endogenous dopamine kinetics of [3H]N-methylspiperone and [3H]raclopride binding in the rat brain. Synapse 9: 188–194PubMedGoogle Scholar
  36. Zetterström T, Sharp T, Marsden CA, Ungerstedt U (1983) In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes after D- amphetamine. J Neurochem 41: 1769–1773PubMedGoogle Scholar

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

Personalised recommendations