Abstract
Chronic nicotine upregulates central nicotinic acetylcholine receptors (nAChRs), a plasticity process thought to contribute to its addictive properties. To analyze this process in vivo, we chronically exposed mice to nicotine using minipump delivering nicotine at concentrations close to those found in tobacco smokers. Binding studies show upregulation of high-affinity nAChRs after 21 days of treatment in cortical areas, caudate putamen, nucleus accumbens, hippocampus, ventral tegmental area, and superior colliculi. No upregulation was observed in thalamus and discrete cortical areas. Using wild type and alpha 6-/- mice, we observed a downregulation of alpha 6*-nAChRs in superior colliculi and no effects in other structures. The complex pattern of upregulation/downregulation observed in this study depends on both nAChR composition and regional distribution.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoradiography / methods
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Brain / cytology
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Brain / drug effects*
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Brain / metabolism
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Cells, Cultured
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Cerebral Cortex / cytology
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Cerebral Cortex / drug effects*
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Cerebral Cortex / metabolism
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Down-Regulation / drug effects
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Hippocampus / cytology
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Hippocampus / drug effects
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Hippocampus / metabolism
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Injections, Subcutaneous
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nicotine / administration & dosage
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Nicotine / pharmacology*
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Nicotinic Agonists / administration & dosage
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Nicotinic Agonists / pharmacology
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Nucleus Accumbens / cytology
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Nucleus Accumbens / drug effects
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Nucleus Accumbens / metabolism
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Putamen / cytology
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Putamen / drug effects
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Putamen / metabolism
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Receptors, Nicotinic / genetics
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Receptors, Nicotinic / metabolism*
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Superior Colliculi / cytology
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Superior Colliculi / drug effects
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Superior Colliculi / metabolism
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Up-Regulation / drug effects
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Ventral Tegmental Area / cytology
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Ventral Tegmental Area / drug effects
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Ventral Tegmental Area / metabolism
Substances
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Nicotinic Agonists
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Receptors, Nicotinic
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alpha6beta2 nicotinic acetylcholine receptor
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nicotinic receptor alpha4beta2
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Nicotine