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Pharmacologic evidence for direct dopaminergic regulation of striatal acetylcholine release
Authors:J M Gorell  B Czarnecki
Affiliation:1. Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA;2. Department of Psychology, Princeton University, Princeton, NJ 08544, USA;1. Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA;2. Department of Psychology, Princeton University, Princeton, NJ 08544, USA;3. Center for Neuroscience, University of California, Davis, Davis, CA 95616, USA;4. Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, CA 95616, USA;5. Department of Ophthalmology and Vision Science, University of California, Davis, Davis, CA 95616, USA;6. Department of Physics and Astronomy, University of California, Davis, Davis, CA 95616, USA;7. Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA;1. Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA;2. Department of Psychology, Princeton University, Princeton, NJ 08544, USA
Abstract:This study was done to provide pharmacologic evidence for the location of those striatal dopamine D-1 and D-2 receptors that participate in the regulation of local acetylcholine (ACh) release. Striatal tissue slices from adult male Sprague-Dawley rats were preloaded with [3H]choline and superfused in separate experiments with buffer containing either: a D-2-specific agonist (LY141865 or LY171555), a D-2 specific antagonist (L-sulpiride), a D-1 specific agonist (SKF38393), or a D-1 antagonist (SCH23390), in the presence or absence of tetrodotoxin (TTX), used to block interneuronal activity. With either D-2 agonist there was a dose-dependent decrease in K+-stimulated [3H]ACh release, maximally at 5 X 10(-7)-10(-6) M [agonist] and to the same extent with each drug. Both SKF38393 and SCH23390 increased [3H]ACh release at tested concentrations of these agents. Results were unchanged when any of the drugs used was superfused in the presence of TTX, 5 X 10(-7) M. These data are consistent with the hypothesis that populations of striatal D-1 and D-2 receptors exist on local cholinergic neurons, where they regulate ACh release. Alternative interpretations are discussed.
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