Department of Pharmacology, University of Tennessee Health Science Center, 71 S. Manassas St., Room 205 Translational Science Research Building, Memphis, TN, 38163, USA.
Sci Rep. 2017 Aug 14;7(1):8052. doi: 10.1038/s41598-017-08291-5.
Both social environment and genetic factors are critical for smoking initiation and nicotine addiction. We reported that rats developed conditioned flavor (i.e., taste and odor) aversion to intravenously self-administered (IVSA) nicotine, and that social learning promoted nicotine IVSA with flavor cues. We thus tested the hypothesis that socially acquired nicotine IVSA is a heritable trait by using female rats of six inbred strains and six F1 hybrids. Each strain was tested for 10 daily IVSA sessions. We found that the intake of nicotine (15 and 30 μg/kg/inf) varied among these strains by 33.7-56.6-fold. The heritability of nicotine intake was estimated to be 0.54-0.65. Further, there was a strong correlation in nicotine intake (R = 0.85, p < 0.0001) between the two nicotine doses. Another cohort of rats was given three daily IVSA sessions followed by five sessions that tested conditioned flavor aversion. Nicotine intake was highly correlated with the extinction of the conditioned aversion (R = 0.58, p < 0.005). These data showed that nicotine intake in the socially acquired nicotine self-administration model is controlled by genetic factors and that the role of social learning is likely in facilitating the extinction of conditioned aversive response to nicotine.
社会环境和遗传因素对于吸烟的开始和尼古丁成瘾都至关重要。我们曾报道过，大鼠对静脉内自我给药（IVSA）的尼古丁产生了条件性味道（即味觉和嗅觉）厌恶，而社会学习则促进了与味道线索相关的尼古丁 IVSA。因此，我们通过使用六种近交系大鼠和六种 F1 杂种大鼠来检验社会获得性尼古丁 IVSA 是一种可遗传特征的假设。每种品系都接受了 10 天的 IVSA 测试。我们发现，这些品系对尼古丁（15 和 30μg/kg/inf）的摄入差异高达 33.7-56.6 倍。尼古丁摄入的遗传力估计为 0.54-0.65。此外，两种尼古丁剂量之间的尼古丁摄入存在很强的相关性（R=0.85，p<0.0001）。另一组大鼠接受了三次每日 IVSA 测试，随后进行了五次测试条件性味觉厌恶的测试。尼古丁摄入与条件性厌恶的消退高度相关（R=0.58，p<0.005）。这些数据表明，在社会获得性尼古丁自我给药模型中，尼古丁的摄入受遗传因素控制，而社会学习的作用可能在于促进对尼古丁的条件性厌恶反应的消退。
