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Journal of Nuclear Medicine

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Meeting ReportOral Presentations - Physicians/Scientists/Pharmacists

Chronic exposure to Δ9-tetrahydrocannabinol induces increased dopamine transporter availability

Dorien Vercammen, Cindy Casteels, Karolien Goffin, Peter Vermaelen, Bert Vanbilloen, Guy Bormans and Koen Van Laere
Journal of Nuclear Medicine May 2006, 47 (suppl 1) 10P;
Dorien Vercammen
1Nuclear Medicine, University Hospital Leuven, Leuven, Belgium
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Cindy Casteels
1Nuclear Medicine, University Hospital Leuven, Leuven, Belgium
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Karolien Goffin
1Nuclear Medicine, University Hospital Leuven, Leuven, Belgium
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Peter Vermaelen
1Nuclear Medicine, University Hospital Leuven, Leuven, Belgium
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Bert Vanbilloen
1Nuclear Medicine, University Hospital Leuven, Leuven, Belgium
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Guy Bormans
2Laboratory for Radiopharmaceutical Chemistry, K.U.Leuven, Leuven, Belgium
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Koen Van Laere
1Nuclear Medicine, University Hospital Leuven, Leuven, Belgium
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Abstract

27

Objectives: A tight association exists between the brain cannabinoid system and dopaminergic circuits involved in addiction, schizophrenia and movement disorders. Ex vivo measurements have shown that delta-9-tetrahydrocannabinol (Δ9-THC), a cannabinoid-1 receptor agonist and the major active constituent of marijuana, may alleviate reduced striatal dopamine transporter (DAT) density in schizophrenia (Dean,Biol Psych 2003). Cannabinoids have been reported to be neuroprotective in acute and chronic neurodegeneration, e.g. against 6-hydroxydopamine toxicity in the model for PD (Lastres-Becker,Neurobiol Dis 2005). The aim of this study was to quantify the effect of Δ9-THC on in vivo striatal and midbrain DAT binding by microPET.

Methods: Six healthy Wistar rats (female, 200-250g, age 15-18w) were investigated in baseline condition, after acute (single injection of 0.5mg/kg IV) and chronic (2 weeks, 3mg/kg IP daily) administration of Δ9-THC (Lipomed, Switzerland, purity > 97 %). Behavioral testing using the cylinder test was done at day 0,2,7 and 14. Anesthesia was done using 60 mg/kg pentobarbital IP. After tail vein IV bolus injection of 17 MBq of 18F-FECNT, static acquisitions (40 min, start 3h p.i.) were conducted on a FOCUS microPET system. FPB reconstructed data were anatomically standardized and analyzed using a predefined VOI approach. Regional DAT binding ((activity-cerebellum)/cerebellum) was analyzed using paired t-tests.

Results: Cylinder tests showed increasing akinesia with chronic Δ9-THC exposure. FECNT binding in the striatum and substantia nigra was not affected by a single injection of Δ9-THC (all p>0.1). However, chronic Δ9-THC administration resulted in augmented DAT binding in the striatum, compared to baseline (+13 %, p=0.04). In the midbrain, FECNT binding was not affected.

Conclusions: Chronic Δ9-THC exposure induces DAT expression and/or affinity increases. These first-time in vivo findings contradict a possible role of Δ9-THC as DAT inhibitor to explain increases in extracellular dopamine levels (Sakurai, Pharm Biochem Behav 1989), but support alternative mechanisms e.g. by changes in cell firing (Pistis, Brain Res 2002; French, Neuroreport 1997). This quantitative pharmacological effect needs to be considered when investigating the neuroprotective effect of cannabinoid agonists in animal models of PD using DAT as biomarker, in the evaluation of cannabinoid-dopamine interactions in drug abuse and schizophrenia, or in evaluating patients for neurodegenerative movement disorders with previous chronic exposure to cannabis.

Research Support (if any): Supported by: EU FP6 DIMI project, K.U.Leuven Fund OT 05/59, IWT Flanders-Animone and FWO G.0548.06.

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Journal of Nuclear Medicine
Vol. 47, Issue suppl 1
May 1, 2006
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Chronic exposure to Δ9-tetrahydrocannabinol induces increased dopamine transporter availability
Dorien Vercammen, Cindy Casteels, Karolien Goffin, Peter Vermaelen, Bert Vanbilloen, Guy Bormans, Koen Van Laere
Journal of Nuclear Medicine May 2006, 47 (suppl 1) 10P;

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Chronic exposure to Δ9-tetrahydrocannabinol induces increased dopamine transporter availability
Dorien Vercammen, Cindy Casteels, Karolien Goffin, Peter Vermaelen, Bert Vanbilloen, Guy Bormans, Koen Van Laere
Journal of Nuclear Medicine May 2006, 47 (suppl 1) 10P;
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