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Metabolic Changes in the Rodent Brain after Acute Administration of Salvinorin A



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B Academy of Molecular Imaging 2009 Published Online 9 January 2009 Mol Imaging Biol 2009 11 137Y143 DOI 10 1007 s11307 008 0192 x BRIEF ARTICLE Metabolic Changes in the Rodent Brain after Acute Administration of Salvinorin A Jacob M Hooker 1 Vinal Patel 1 Shiva Kothari 1 Wynne K Schiffer1 Medical Department Brookhaven National Laboratory Upton NY 11973 USA Abstract Purpose Salvinorin A SA is a potent and highly selective kappa opioid receptor KOR agonist with rapid kinetics and commensurate behavioral effects however brain regions associated with these effects have not been determined Procedures Freely moving adult male rats were given SA intraperitoneally during uptake and trapping of the brain metabolic radiotracer 2 deoxy 2 F 18 fluoro D glucose FDG followed by image acquisition in a dedicated animal positron emission tomography PET system Age matched control animals received vehicle treatment Animal behavior during FDG uptake was recorded digitally and later analyzed for locomotion Group differences in regional FDG uptake normalized to whole brain were determined using Statistical Parametric Mapping SPM and verified by region of interest ROI analysis Results SA treated animals demonstrated significant increases in FDG uptake compared to controls in several brain regions associated with the distribution of KOR such as the periaqueductal grey bed nucleus of the stria terminalis and the cerebellar vermis as well as in the hypothalamus Significant bilateral activations were also observed in the auditory sensory and frontal cortices Regional decreases in metabolic demand were observed bilaterally in the dorsolateral striatum and hippocampus Locomotor activity did not differ between SA and vehicle during FDG uptake Conclusions We have provided the first extensive maps of cerebral metabolic activation due to the potent opioid agonist salvinorin A A major finding from our small animal PET studies using FDG was that neural circuits affected by SA may not be limited to



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