title: α2-Null mutant mice have altered levels of neuronal activity in restricted midbrain and limbic brain regions during nicotine withdrawal as demonstrated by cfos expression.
abstract: Neuronal nicotinic acetylcholine receptors (nAChRs) are the primary binding sites for nicotine within the brain. Using alpha(α)2 nAChR subunit-null mutant mice, the current study evaluates whether the absence of this gene product during mecamylamine-precipitated nicotine withdrawal eliminates neuronal activity within selective midbrain and limbic brain regions, as determined by the expression of the immediate early gene, cfos. Our results demonstrate that nicotine withdrawal enhances neuronal activity within the interpeduncular nucleus and dorsal hippocampus, which is absent in mice null for α2-containing nAChRs. In contrast, we observe that α2-null mutant mice exhibit a suppression of neuronal activity in the dentate gyrus in mice undergoing nicotine withdrawal. Interestingly, α2-null mutant mice display potentiated neuronal activity specifically within the stratum lacunosum moleculare layer of the hippocampus, independent of nicotine withdrawal. Overall, our findings demonstrate that α2-null mutant mice have altered cfos expression in distinct populations of neurons within selective midbrain and limbic brain structures that mediate baseline and nicotine withdrawal-induced neuronal activity.
authors.affiliation: Department of Psychiatry, University of California, Los Angeles, MRL Building, Room 2557, 675 Charles E. Young Drive South, Los Angeles, CA 90095, United States.
authors.forename: Montana
authors.initials: M
authors.lastname: Upton
authors.affiliation: Department of Psychiatry, University of California, Los Angeles, MRL Building, Room 2557, 675 Charles E. Young Drive South, Los Angeles, CA 90095, United States. Electronic address: lotfipour@gmail.com.
authors.forename: Shahrdad
authors.initials: S
authors.lastname: Lotfipour
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D008032:Limbic System / Q000166:cytology* / Q000502:physiology; D008297:Male; D008636:Mesencephalon / Q000166:cytology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D014029:Tobacco Use Disorder / Q000378:metabolism*
chemical_list: C000603869:CHRNA2 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D011978:Receptors, Nicotinic
keywords: Addiction; Chrna2; Hippocampus; Interpeduncular nucleus; Neuronal activity; Nicotine withdrawal