title: Nicotine addiction reduces the large-conductance Ca(2+)-activated potassium channels expression in the nucleus accumbens.
abstract: Large-conductance Ca(2+)-activated K(+) channels (BKCa) are widely expressed in the central nervous system and play important roles in neural activities. Nicotine exposure leads to long-lasting changes in behavioral and neuronal plasticity. However, little is known the roles of BKCa in the development of nicotine addiction. In the present study, a significant reduction in BKCa channel expression was found in nucleus accumbens (NAc) from nicotine addiction mice. Whole-cell patch-clamp recordings from NAc neurons of the addicted animals revealed a pronounced reduction in the fast after-hyperpolarization of action potentials mediated by BKCa channels that led to hyperexcitability of the NAc neurons. Activation of BKCa channels in the NAc reversed drug-seeking behaviors which were detected by conditioned place preference test. Furthermore, knockdown of BKCa channels using short hairpin RNAs significantly increased the drug-seeking behavior. These findings provide direct evidence that alterations of BKCa channels in the NAc play critical roles in the development of nicotine addiction and that modulation of the BKCa channels may be potential therapeutics for drug addiction.
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, No 17 Changle West Road, Xi'an, 710032, Shaanxi Province, People's Republic of China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Wu
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Guo
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.forename: Qian
authors.initials: Q
authors.lastname: Song
authors.forename: Shui-Bing
authors.initials: SB
authors.lastname: Liu
authors.forename: Da-Qing
authors.initials: DQ
authors.lastname: Zhao
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Zhao
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003214:Conditioning, Classical / Q000187:drug effects; D015536:Down-Regulation; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology*; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation; D017136:Ion Transport; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012201:Reward; D014029:Tobacco Use Disorder / Q000235:genetics / Q000378:metabolism*
chemical_list: C530995:BKCa protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D009538:Nicotine; D011188:Potassium; D002118:Calcium