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.
J Neurosci. 2013 May 1;33(18):7728-41. doi: 10.1523/JNEUROSCI.4731-12.2013.
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.
基线和尼古丁调节的行为在携带烟碱型乙酰胆碱受体（nAChR）亚基基因α2（Chrna2）缺失突变等位基因的小鼠中进行了评估。Chrna2（-/-）纯合子小鼠具有活力，表现出预期的性别和孟德尔基因型比例，并且没有明显的神经解剖学异常。一系列旨在评估焦虑（高架十字迷宫和明暗箱）、运动协调（狭窄豆荚穿越和步态）和运动活动等基因型依赖性影响的行为测试，未发现突变小鼠与年龄匹配的野生型同窝仔鼠之间存在显著差异。此外，一组测量特征的测试，如身体位置、自发活动、呼吸、震颤、身体张力和惊跳反应，显示 Chrna2 缺失突变小鼠的反应正常。然而，Chrna2（-/-）小鼠确实表现出轻微的运动或协调表型（在加速转棒测试中摔倒的潜伏期降低），并且在热板试验中对尼古丁诱导的镇痛作用更为敏感。与野生型相比，Chrna2（-/-）小鼠表现出增强的尼古丁自我给药和戒断行为，并且表现出对尼古丁促进的线索性、但不是痕迹或情境性恐惧条件反射的性别依赖性增强。总体而言，我们的结果表明，丢失小鼠 nAChR α2 亚基对基础行为的影响非常有限，但确实导致几种尼古丁调节行为的增强。
