Department of Biobehavioral Health, Penn State University, University Park, PA, USA.
Department of Biobehavioral Health, Penn State University, University Park, PA, USA.
Brain Res Bull. 2018 Apr;138:50-55. doi: 10.1016/j.brainresbull.2017.06.010. Epub 2017 Jun 15.
Adolescence is a period of high risk for the initiation of nicotine product usage and exposure to traumatic events. In parallel, nicotine exposure has been found to age-dependently modulate acquisition of contextual fear memories; however, it is unknown if adolescent nicotine exposure alters extinction of fear related memories. Age-related differences in sensitivity to the effects of nicotine on fear extinction could increase or decrease susceptibility to anxiety disorders. In this study, we examined the effects of acute nicotine administration on extinction and spontaneous recovery of contextual fear memories in pre-adolescent (PND 23), late adolescent (PND 38), and adult (PND 53) C57B6/J mice. Mice were first trained in a background contextual fear conditioning paradigm and given an intraperitoneal injection of one of four doses of nicotine (0.045, 0.09, 0.18, or 0.36mg/kg, freebase) prior to subsequent extinction or spontaneous recovery sessions. Results indicated that all acute nicotine doses impaired extinction of contextual fear in adult mice. Late adolescent mice exhibited impaired extinction of contextual fear only following higher doses of acute nicotine, and extinction of contextual fear was unaffected by acute nicotine exposure in pre-adolescent mice. Finally, acute nicotine exposure enhanced spontaneous recovery of fear memory, but only in adult mice. Overall, our results suggest that younger mice were less sensitive to nicotine's impairing effects on extinction of contextual fear and to nicotine's enhancing effects on spontaneous recovery of contextual fear memory.
青春期是开始使用尼古丁产品和接触创伤性事件的高风险期。与此同时，研究发现，尼古丁暴露会随着年龄的增长而调节情景性恐惧记忆的获得；然而，目前尚不清楚青少年尼古丁暴露是否会改变与恐惧相关的记忆的消退。青少年尼古丁暴露对恐惧消退效果的敏感性的年龄相关差异可能会增加或降低焦虑障碍的易感性。在这项研究中，我们研究了急性尼古丁给药对未成年（PND 23）、青少年晚期（PND 38）和成年（PND 53）C57B6/J 小鼠的情景性恐惧记忆消退和自发恢复的影响。首先，将小鼠置于背景情景性恐惧条件化训练范式中，然后在随后的消退或自发恢复阶段，给它们腹腔内注射四种剂量的尼古丁（0.045、0.09、0.18 或 0.36mg/kg，游离碱）之一。结果表明，所有急性尼古丁剂量都损害了成年小鼠的情景性恐惧消退。只有在较高剂量的急性尼古丁作用下，青少年晚期小鼠才会出现情景性恐惧消退受损，而在未成年小鼠中，急性尼古丁暴露对情景性恐惧消退没有影响。最后，急性尼古丁暴露增强了恐惧记忆的自发恢复，但仅在成年小鼠中出现。总体而言，我们的研究结果表明，年幼的小鼠对尼古丁对情景性恐惧消退的损害作用以及对情景性恐惧记忆自发恢复的增强作用的敏感性较低。
