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Interference of anaesthetics with radioligand binding in neuroreceptor studies

  • Betina ElfvingEmail author
  • Berith Bjørnholm
  • Gitte Moos Knudsen
Short Communication

Abstract

Evaluations of new emission tomography ligands are usually carried out in animals. In order to keep the animals in a restricted position during the scan session, anaesthesia is almost inevitable. In ex vivo rat studies we investigated the interference of ketamine/xylazine, zoletile mixture, isoflurane and halothane with the serotonin re-uptake site, the serotonin2A receptor and the dopamine re-uptake site by use of [3H]-(S)-citalopram, [18F]altanserin and [125I]PE2I, respectively. Ketamine/xylazine decreased the target-to-background ratio (mean ± SD) of [3H]-(S)-citalopram from 1.5±0.19 to 0.81±0.19 (P<0.05), whereas isoflurane and halothane increased the ratio from 1.5±0.19 to 1.9±0.24 and 2.1±0.13 (P<0.05), respectively. Only with the zoletile mixture did the ratio remain unaltered. None of the tested anaesthetics affected the target-to-background ratio of [18F]altanserin. The [125I]PE2I target-to-background ratio decreased with both ketamine/xylazine (from 12.4±0.81 to 10.1±1.4, P<0.05) and isoflurane (from 12.4±0.81 to 9.5±1.1, P<0.05) treated rats, whereas treatment with zoletile mixture and halothane left the ratio unaltered. It is concluded that prior to performance of neuroreceptor radioligand studies, the possible interaction between radioligands and anaesthetics should be carefully evaluated.

Keywords

(S)-citalopram PE2I Altanserin Anaesthesia 

Notes

Acknowledgements

This work was supported by a research grant from The 1991 Pharmacy Foundation, Health Insurance Fund and the Lundbeck Foundation. We thank Denis Guilloteau, Service de Médecine Nucléaire, Tours, France for labelling [125I]PE2I. The excellent technical assistance by Inge Møller, Neurobiology Research Laboratory, University Hospital Rigshospitalet, Denmark is much appreciated.

References

  1. 1.
    Elfving B, Bjørnholm B, Knudsen G. Predosing with the unlabeled "inactive" enantiomer as a tool for improvement of the PET signal. Synapse 2002; 46:125–127.CrossRefPubMedGoogle Scholar
  2. 2.
    Tao R, Auerbach SB. Anesthetics block morphine-induced increases in serotonin release in rat CNS. Synapse 1994; 18:307–314.PubMedGoogle Scholar
  3. 3.
    Tsukada H, Nishiyama S, Kakiuchi T, Ohba H, Sato K, Harada N. Ketamine alters the availability of striatal dopamine transporter as measured by [11C]β-CFT and [11C]β-CIT-FE in the monkey brain. Synapse 2001; 42:273–280.CrossRefPubMedGoogle Scholar
  4. 4.
    Minami K, Minami M, Harris RA. Inhibition of 5-hydroxytryptamine type 2A receptor-induced currents by n-alcohols and anesthetics. J Pharmacol Exp Ther 1997; 281:1136–1143.PubMedGoogle Scholar
  5. 5.
    Rao TS, Contreras PC, Cler JA, et al. Contrasting neurochemical interactions of tiletamine, a potent phencyclidine (PCP) receptor ligand, with the N-methyl-d-aspartate-coupled and -uncoupled PCP recognition sites. J Neurochem 1991; 56:890–897.PubMedGoogle Scholar
  6. 6.
    Martin DC, Adams RJ, Aronstam RS. The influence of isoflurane on the synaptic activity of 5-hydroxytryptamine. Neurochem Res 1990; 15:969–973.PubMedGoogle Scholar
  7. 7.
    Votaw JR, Byas-Smith M, Martarello L, Howell LL, Kilts CD, Wilcox K, Goodman MM. Interaction of isoflurane and sevoflurane with the dopamine transporter. J Nucl Med Suppl 2001; 42:213P.Google Scholar
  8. 8.
    Wollmer P, Moresco RM, Simonelli P, et al. Evaluation of [O-methyl-11C]fluvoxamine as a tracer for serotonin re-uptake sites. Nucl Med Biol 2000; 27:177–181.CrossRefPubMedGoogle Scholar
  9. 9.
    Guilloteau D, Emond P, Baulieu JL, et al. . Exploration of the dopamine transporter: in vitro and in vivo characterization of a high-affinity and high-specificity iodinated tropane derivative (E)-N-(3-iodoprop-2-enyl)-2β-carbomethoxy-3 β -(4'-methylphenyl)nor-tropane (PE2I). Nucl Med Biol 1998; 25:331–337.PubMedGoogle Scholar
  10. 10.
    Poyot T, Conde F, Gregoire MC, et al. Anatomic and biochemical correlates of the dopamine transporter ligand [11C]PE2I in normal and parkinsonian primates: comparison with 6-[18F]fluoro-l-dopa. J Cereb Blood Flow Metab 2001; 21:782–792.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Betina Elfving
    • 1
    Email author
  • Berith Bjørnholm
    • 2
  • Gitte Moos Knudsen
    • 1
  1. 1.Neurobiology Research Unit N9201University hospital RigshospitaletCopenhagenDenmark
  2. 2.Department of Computational ChemistryH. Lundbeck A/SCopenhagen-ValbyDenmark

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