title: Targeted deletion of the mouse α2 nicotinic acetylcholine receptor subunit gene (Chrna2) potentiates nicotine-modulated behaviors.
abstract: Baseline and nicotine-modulated behaviors were assessed in mice harboring a null mutant allele of the nicotinic acetylcholine receptor (nAChR) subunit gene α2 (Chrna2). Homozygous Chrna2(-/-) mice are viable, show expected sex and Mendelian genotype ratios, and exhibit no gross neuroanatomical abnormalities. A broad range of behavioral tests designed to assess genotype-dependent effects on anxiety (elevated plus maze and light/dark box), motor coordination (narrow bean traverse and gait), and locomotor activity revealed no significant differences between mutant mice and age-matched wild-type littermates. Furthermore, a panel of tests measuring traits, such as body position, spontaneous activity, respiration, tremors, body tone, and startle response, revealed normal responses for Chrna2-null mutant mice. However, Chrna2(-/-) mice do exhibit a mild motor or coordination phenotype (a decreased latency to fall during the accelerating rotarod test) and possess an increased sensitivity to nicotine-induced analgesia in the hotplate assay. Relative to wild-type, Chrna2(-/-) mice show potentiated nicotine self-administration and withdrawal behaviors and exhibit a sex-dependent enhancement of nicotine-facilitated cued, but not trace or contextual, fear conditioning. Overall, our results suggest that loss of the mouse nAChR α2 subunit has very limited effects on baseline behavior but does lead to the potentiation of several nicotine-modulated behaviors.
authors: Department of Psychiatry and Biobehavioral Sciences, Hatos Center for Neuropharmacology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California 90024, USA. shahrdad@ucla.edu
authors: Shahrdad
authors: S
authors: Lotfipour
authors: Janet S
authors: JS
authors: Byun
authors: Prescott
authors: P
authors: Leach
authors: Christie D
authors: CD
authors: Fowler
authors: Niall P
authors: NP
authors: Murphy
authors: Paul J
authors: PJ
authors: Kenny
authors: Thomas J
authors: TJ
authors: Gould
authors: Jim
authors: J
authors: Boulter
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D003214:Conditioning, Classical / Q000187:drug effects; D004334:Drug Administration Schedule; D004924:Escape Reaction / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000009:adverse effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time; D011978:Receptors, Nicotinic / Q000172:deficiency*; D012018:Reflex / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000503:physiopathology*
chemical_list: D018377:Neurotransmitter Agents; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D009538:Nicotine; D009020:Morphine
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