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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 6/2010

01-06-2010 | Original Article

The effect of anaesthesia on [18F]MK-9470 binding to the type 1 cannabinoid receptor in the rat brain

Authors: Cindy Casteels, Guy Bormans, Koen Van Laere

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2010

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Abstract

Purpose

Small animal PET can be applied to study molecular processes in animal models of a variety of human diseases. In order to keep the animals in a restricted position during imaging, anaesthesia is in many instances inevitable. Using small animal PET and ex vivo autoradiography, we examined the influence of pentobarbital and isoflurane anaesthesia on the rat brain uptake of [18F]MK-9470, a radioligand for the type 1 cannabinoid receptor.

Methods

PET imaging was performed on adult Wistar rats under pentobarbital (n = 6) and isoflurane anaesthesia (n = 7), and under control conditions (free moving during tracer uptake, n = 8). Parametric PET images were generated, anatomically standardized and analysed by voxel-based Statistical Parametric Mapping and a predefined volume of interest approach. Immediately after in vivo PET, brains were processed for ex vivo autoradiography using manually placed regions of interest. An extra group (n = 6) was included ex vivo, in which animals were intravenously injected without the use of anaesthetics.

Results

Using in vivo and ex vivo molecular imaging techniques, no significant changes in absolute [18F]MK-9470 uptake were present in the brain of pentobarbital and isoflurane rats as compared to control conditions. Relative [18F]MK-9470 uptake PET values obtained applying global scaling were, however, decreased in the cortex under both anaesthetics (pentobarbital: −13.3±1.4%; isoflurane −8.7 ± 3.1%), while an increase was seen in the cerebellum by 13.5 ± 4.0% and 13.9 ± 4.1% under pentobarbital and isoflurane, respectively. Ex vivo results were in agreement with in vivo findings.

Conclusion

These findings suggest a similar, regionally specific interference of pentobarbital and isoflurane anaesthesia with in vivo CB1 receptor imaging using [18F]MK-9470.
Literature
1.
Di Marzo V, Melck D, Bisogno T, De Petrocellis L. Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action. Trends Neurosci 1998;21:521–8.CrossRefPubMed
2.
Van Laere K. In vivo imaging of the endocannabinoid system: a novel window to a central modulatory mechanism in humans. Eur J Nucl Med Mol Imaging 2007;34:1719–26.CrossRefPubMed
3.
4.
Bahr BA, Karanian DA, Makanji SS, Makriyannis A. Targeting the endocannabinoid system in treating brain disorders. Expert Opin Investig Drugs 2006;15:351–65.CrossRefPubMed
5.
Cherry SR, Gambhir SS. Use of positron emission tomography in animal research. ILAR J 2001;42:219–32.PubMed
6.
Momosaki S, Hatano K, Kawasumi Y, Kato T, Hosoi R, Kobayashi K, et al. Rat-PET study without anesthesia: anesthetics modify the dopamine D1 receptor binding in rat brain. Synapse 2004;54:207–13.CrossRefPubMed
7.
Votaw JR, Byas-Smith MG, Voll R, Halkar R, Goodman MM. Isoflurane alters the amount of dopamine transporter expressed on the plasma membrane in humans. Anesthesiology 2004;101:1128–35.CrossRefPubMed
8.
Kobayashi K, Inoue O, Watanabe Y, Onoe H, Långström B. Difference in response of D2 receptor binding between 11C-N-methylspiperone and 11C-raclopride against anesthetics in rhesus monkey brain. J Neural Transm Gen Sect 1995;100:147–51.CrossRefPubMed
9.
Toyama H, Ichise M, Liow JS, Modell KJ, Vines DC, Esaki T, et al. Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography. J Nucl Med 2004;45:1398–405.PubMed
10.
Zeller A, Arras M, Jurd R, Rudolph U. Identification of a molecular target mediating the general anesthetic actions of pentobarbital. Mol Pharmacol 2007;71:852–9.CrossRefPubMed
11.
Jones MV, Brooks PA, Harrison NL. Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics. J Physiol 1992;449:279–93.PubMed
12.
Yang J, Zorumski CF. Effects of isoflurane on N-methyl-D-aspartate gated ion channels in cultured rat hippocampal neurons. Ann N Y Acad Sci 1991;625:287–9.CrossRefPubMed
13.
Votaw J, Byas-Smith M, Hua J, Voll R, Martarello L, Levey AI, et al. Interaction of isoflurane with the dopamine transporter. Anesthesiology 2003;98:404–11.CrossRefPubMed
14.
Burns HD, Van Laere K, Sanabria-Bohórquez S, Hamill TG, Bormans G, Eng WS, et al. [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proc Natl Acad Sci U S A 2007;104:9800–5.CrossRefPubMed
15.
Goffin K, Bormans G, Casteels C, Bosier B, Lambert DM, Grachev ID, et al. An in vivo [(18)F]MK-9470 microPET study of type 1 cannabinoid receptor binding in Wistar rats after chronic administration of valproate and levetiracetam. Neuropharmacology 2008;54:1103–6.CrossRefPubMed
16.
Casteels C, Vermaelen P, Nuyts J, Van Der Linden A, Baekelandt V, Mortelmans L, et al. Construction and evaluation of multitracer small-animal PET probabilistic atlases for voxel-based functional mapping of the rat brain. J Nucl Med 2006;47:1858–66.PubMed
17.
van Kuyck K, Casteels C, Vermaelen P, Bormans G, Nuttin B, Van Laere K. Motor- and food-related metabolic cerebral changes in the activity-based rat model for anorexia nervosa: a voxel-based microPET study. Neuroimage 2007;35:214–21.CrossRefPubMed
18.
Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, et al. Cannabinoid receptor localization in brain. Proc Natl Acad Sci U S A 1990;87:1932–6.CrossRefPubMed
19.
Paxinos G, Watson C. The rat brain in stereotaxic coordinates. New York: Academic; 1998.
20.
Hildebrandt IJ, Su H, Weber WA. Anesthesia and other considerations for in vivo imaging of small animals. ILAR J 2008;49:17–26.PubMed
21.
Zhang Y, Laster MJ, Hara K, Harris RA, Eger EI 2nd, Stabernack CR, et al. Glycine receptors mediate part of the immobility produced by inhaled anesthetics. Anesth Analg 2003;96:97–101.CrossRefPubMed
22.
Carlà V, Moroni F. General anaesthetics inhibit the responses induced by glutamate receptor agonists in the mouse cortex. Neurosci Lett 1992;146:21–4.CrossRefPubMed
23.
Kimbro JR, Kelly PJ, Drummond JC, Cole DJ, Patel PM. Isoflurane and pentobarbital reduce AMPA toxicity in vivo in the rat cerebral cortex. Anesthesiology 2000;92:806–12.CrossRefPubMed
24.
Moody EJ, Suzdak PD, Paul SM, Skolnick P. Modulation of the benzodiazepine/gamma-aminobutyric acid receptor chloride channel complex by inhalation anesthetics. J Neurochem 1988;51:1386–93.CrossRefPubMed
25.
Huidobro-Toro JP, Bleck V, Allan AM, Harris RA. Neurochemical actions of anesthetic drugs on the gamma-aminobutyric acid receptor-chloride channel complex. J Pharmacol Exp Ther 1987;242:963–9.PubMed
26.
Longoni B, Demontis GC, Olsen RW. Enhancement of gamma-aminobutyric acidA receptor function and binding by the volatile anesthetic halothane. J Pharmacol Exp Ther 1993;266:153–9.PubMed
27.
Mody I, Tanelian DL, MacIver MB. Halothane enhances tonic neuronal inhibition by elevating intracellular calcium. Brain Res 1991;538:319–23.CrossRefPubMed
28.
Gage PW, Robertson B. Prolongation of inhibitory postsynaptic currents by pentobarbitone, halothane and ketamine in CA1 pyramidal cells in rat hippocampus. Br J Pharmacol 1985;85:675–81.PubMed
29.
Nakahiro M, Yeh JZ, Brunner E, Narahashi T. General anesthetics modulate GABA receptor channel complex in rat dorsal root ganglion neurons. FASEB J 1989;3:1850–4.PubMed
30.
Wakamori M, Ikemoto Y, Akaike N. Effects of two volatile anesthetics and a volatile convulsant on the excitatory and inhibitory amino acid responses in dissociated CNS neurons of the rat. J Neurophysiol 1991;66:2014–21.PubMed
31.
Gutiérrez A, Khan ZU, De Blas AL. Immunocytochemical localization of gamma 2 short and gamma 2 long subunits of the GABAA receptor in the rat brain. J Neurosci 1994;14:7168–79.PubMed
32.
Petralia RS, Wenthold RJ. Light and electron immunocytochemical localization of AMPA-selective glutamate receptors in the rat brain. J Comp Neurol 1992;318:329–54.CrossRefPubMed
33.
Martin LJ, Blackstone CD, Huganir RL, Price DL. Cellular localization of a metabotropic glutamate receptor in rat brain. Neuron 1992;9:259–70.CrossRefPubMed
34.
Moldrich G, Wenger T. Localization of the CB1 cannabinoid receptor in the rat brain. An immunohistochemical study. Peptides 2000;21:1735–42.CrossRefPubMed
35.
Ramani R, Wardhan R. Understanding anesthesia through functional imaging. Curr Opin Anaesthesiol 2008;21:530–6.CrossRefPubMed
36.
Schlünzen L, Cold GE, Rasmussen M, Vafaee MS. Effects of dose-dependent levels of isoflurane on cerebral blood flow in healthy subjects studied using positron emission tomography. Acta Anaesthesiol Scand 2006;50:306–12.CrossRefPubMed
37.
Hansen TD, Warner DS, Todd MM, Vust LJ, Trawick DC. Distribution of cerebral blood flow during halothane versus isoflurane anesthesia in rats. Anesthesiology 1988;69:332–7.CrossRefPubMed
38.
Matta BF, Heath KJ, Tipping K, Summors AC. Direct cerebral vasodilatory effects of sevoflurane and isoflurane. Anesthesiology 1999;91:677–80.CrossRefPubMed
39.
Hendrich KS, Kochanek PM, Melick JA, Schiding JK, Statler KD, Williams DS, et al. Cerebral perfusion during anesthesia with fentanyl, isoflurane, or pentobarbital in normal rats studied by arterial spin-labeled MRI. Magn Reson Med 2001;46:202–6.CrossRefPubMed
40.
Todd MM, Weeks J. Comparative effects of propofol, pentobarbital, and isoflurane on cerebral blood flow and blood volume. J Neurosurg Anesthesiol 1996;8:296–303.CrossRefPubMed
41.
Sanabria-Bohórquez SM, Hamill TG, Goffin K, De Lepeleire I, Bormans G, Burns HD, et al. Kinetic analysis of the cannabinoid-1 receptor PET tracer [(18)F]MK-9470 in human brain. Eur J Nucl Med Mol Imaging, in press. 2009.
42.
Sugiura M, Kawashima R, Sadato N, Senda M, Kanno I, Oda K, et al. Anatomic validation of spatial normalization methods for PET. J Nucl Med 1999;40:317–22.PubMed
43.
Rodríguez de Fonseca F, Cebeira M, Ramos JA, Martín M, Fernández-Ruiz JJ. Cannabinoid receptors in rat brain areas: sexual differences, fluctuations during estrous cycle and changes after gonadectomy and sex steroid replacement. Life Sci 1994;54:159–70.CrossRefPubMed
44.
Westerling P, Lindgren S, Meyerson B. Functional changes in GABAA receptor stimulation during the oestrous cycle of the rat. Br J Pharmacol 1991;103:1580–4.PubMed
45.
Flood P, Daniel D. Pronociceptive actions of isoflurane: a protective role for estrogen. Anesthesiology 2003;99:476–9.CrossRefPubMed
Metadata
Title
The effect of anaesthesia on [18F]MK-9470 binding to the type 1 cannabinoid receptor in the rat brain
Authors
Cindy Casteels
Guy Bormans
Koen Van Laere
Publication date
01-06-2010
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2010
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-010-1383-7

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