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 kappa-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 direct activation or inhibition of kappa-receptor-expressing cells. Instead, salvinorin A may trigger brain circuits that mediate the effects of the drug on cognition, mood, fear and anxiety, and motor output.
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 kappa-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 direct activation or inhibition of kappa-receptor-expressing cells. Instead, salvinorin A may trigger brain circuits that mediate the effects of the drug on cognition, mood, fear and anxiety, and motor output.
Authors: David Y W Lee; Vishnu V R Karnati; Minsheng He; Lee-Yuan Liu-Chen; Leelakrishna Kondaveti; Zhongze Ma; Yulin Wang; Yong Chen; Cecile Beguin; William A Carlezon; Bruce Cohen Journal: Bioorg Med Chem Lett Date: 2005-08-15 Impact factor: 2.823
Authors: David Y W Lee; Zhongze Ma; Lee-Yuan Liu-Chen; Yulin Wang; Yong Chen; William A Carlezon; Bruce Cohen Journal: Bioorg Med Chem Date: 2005-10-01 Impact factor: 3.641
Authors: William E Fantegrossi; Kelly M Kugle; Leander J Valdes; Masato Koreeda; James H Woods Journal: Behav Pharmacol Date: 2005-12 Impact factor: 2.293
Authors: Yong Zhang; Eduardo R Butelman; Stefan D Schlussman; Ann Ho; Mary Jeanne Kreek Journal: Psychopharmacology (Berl) Date: 2005-01-29 Impact factor: 4.530
Authors: William A Carlezon; Cécile Béguin; Jennifer A DiNieri; Michael H Baumann; Michele R Richards; Mark S Todtenkopf; Richard B Rothman; Zhongze Ma; David Y-W Lee; Bruce M Cohen Journal: J Pharmacol Exp Ther Date: 2005-10-13 Impact factor: 4.030
Authors: Elena Prieto; María Collantes; Mercedes Delgado; Carlos Juri; Luis García-García; Francisco Molinet; María E Fernández-Valle; Miguel A Pozo; Belén Gago; Josep M Martí-Climent; José A Obeso; Iván Peñuelas Journal: Eur J Nucl Med Mol Imaging Date: 2011-08-27 Impact factor: 9.236
Authors: Chia Li; Kristen E Pleil; Alice M Stamatakis; Steven Busan; Linh Vong; Bradford B Lowell; Garret D Stuber; Thomas L Kash Journal: Biol Psychiatry Date: 2012-01-05 Impact factor: 13.382
Authors: Frederick A Schroeder; Daniel B Chonde; Misha M Riley; Christian K Moseley; Michael L Granda; Colin M Wilson; Florence F Wagner; Yan-Ling Zhang; Jennifer Gale; Edward B Holson; Stephen J Haggarty; Jacob M Hooker Journal: Neurosci Lett Date: 2013-06-25 Impact factor: 3.046
Authors: Alice M Stamatakis; Dennis R Sparta; Joshua H Jennings; Zoe A McElligott; Heather Decot; Garret D Stuber Journal: Neuropharmacology Date: 2013-06-07 Impact factor: 5.250
Authors: Boris von Reutern; Barbara Grünecker; Behrooz H Yousefi; Gjermund Henriksen; Michael Czisch; Alexander Drzezga Journal: Mol Imaging Biol Date: 2013-10 Impact factor: 3.488
Authors: Thomas L Kash; Kristen E Pleil; Catherine A Marcinkiewcz; Emily G Lowery-Gionta; Nicole Crowley; Christopher Mazzone; Jonathan Sugam; J Andrew Hardaway; Zoe A McElligott Journal: Mol Cells Date: 2014-12-04 Impact factor: 5.034