Effect of duration of haloperidol treatment on DA receptor supersensitization in aging C57BL/6J mice |
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| Authors: | Patrick K. Randall James A. Severson Stanley M. Hurd William O. McClure |
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| Affiliation: | 1. Department of Physiology and Biophysics and Department of Psychiatry, University of Southern California School of Medicine Los Angeles, CA U.S.A.;2. Andrus Gerontology Center and the Department of Biological Sciences, University of Southern California, Los Angeles, CA U.S.A.;1. Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, China;2. Department of Biosciences and Nutrition, Karolinska Institutet Hälsovägen 7C, Neo, 141 57 Huddinge, Sweden;1. Program of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona 31008, Spain;2. Department of Biochemistry and Genetics, School of Science, University of Navarra, Pamplona 31008, Spain;3. Small Molecule Discovery Platform, Molecular Therapeutics Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona 31008, Spain;4. PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, An der Immenburg 4, D-53121 Bonn, Germany;5. Department of Pharmacology, School of Pharmacy, University of Navarra, Pamplona 31008, Spain;6. Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona 08028, Spain;7. IdiSNA, Navarra Institute for Health Research, Pamplona 31008, Spain;1. Program of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona 31008, Spain;2. Department of Biochemistry and Genetics, School of Science, University of Navarra, Pamplona 31008, Spain;3. Department of Pharmacology and Toxicology, School of Pharmacy, University of Navarra, Pamplona 31008, Spain;4. Neuroscience Research Center, Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA;5. Department of Psychobiology, School of Psychology, Complutense University of Madrid, Madrid, Spain;6. Neuropharmacology Laboratory, University Pompeu Fabra, Barcelona, Spain;7. Small Molecule Discovery Platform, Program of Molecular Therapeutics, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona 31008, Spain;8. Centro de Investigación en Red, Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain;9. IdiSNA, Navarra Institute for Health Research, Pamplona 31008, Spain;1. Department of Human Anatomy and Histoembryology, Binzhou Medical University, Yantai, China;2. Department of Pathology, Shandong First Medical University, Jinan, China |
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| Abstract: | Apomorphine-induced behavior, striatal [3H]spiperone binding, and striatal choline acetyltransferase (ChAT) activity were assessed in 6 1/2, 13, and 27-30 month-old male C57BL/6J mice following 0, 30, 60 or 90 days treatment with the dopaminergic (DA) antagonist haloperidol. Both apomorphine-induced behavior and [3H]spiperone binding (Bmax) increased linearly with duration of haloperidol treatment, with no detectable age difference in the degree of supersensitization, although basal receptor density declined with age. Middle- and old-aged mice showed prolonged stereotypic behavior relative to young mice, suggesting slower apomorphine clearance. No differences in ChAT activity were detected with either age or duration of haloperidol treatment. Although the group means of binding and behavior were highly related, the within group correlations were poor. Overall, the results suggest that aged animals are capable of DA receptor supersensitization when given a sufficient stimulus--in this case, relatively long treatment regimes. Previously reported deficits in neuroleptic-induced supersensitization in old mice may be confined to relatively short treatment periods at low doses. |
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| Keywords: | aging neuroleptics [3H]spiperone stereotyped behavior apomorphine DA receptor supersensitization mice |
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