Tian S, Gao J, Han L, Fu J, Li C, Li Z
Department of Physiology, College of Medicine, University of South China, Hengyang, Hunan, PR China.
Neuroscience. 2008 Jun 2;153(4):935-43. doi: 10.1016/j.neuroscience.2008.03.005. Epub 2008 Mar 8.
Clinical observations have shown a link for the high comorbid rate between smoking and psychiatric disorders, including anxiety disorders. However, little is known about the neural mechanism underlying the progression from nicotine dependence to an anxiety disorder. A deficit in fear extinction in general is considered to contribute to anxiety disorders. The aim of the present study is to investigate the effects of chronic nicotine on fear extinction in rats. Rats were administrated s.c. nicotine twice per day for 14 days. Two weeks after the last injection rats received a cued or contextual fear conditioning session. Twenty-four hours and 48 h after conditioning, rats received an extinction training session and an extinction test session, respectively. Percent freezing was assessed during all phases of training. In the cued task, prior chronic nicotine did not affect the acquisition of fear response or the within-session fear extinction, but impaired the between-session fear extinction. In the contextual task, the same nicotine treatment schedule did not affect the acquisition of fear response or the within- and between-session fear extinction, but enhanced the retention of fear conditioning. This prior chronic nicotine-induced deficit in cued fear extinction and/or enhanced fear to context may be one of the critical components that contribute to the progression from nicotine dependence to an anxiety disorder.
临床观察表明，吸烟与包括焦虑症在内的精神疾病之间存在高共病率的联系。然而，对于从尼古丁依赖发展到焦虑症的神经机制知之甚少。一般认为恐惧消退缺陷会导致焦虑症。本研究的目的是调查慢性尼古丁对大鼠恐惧消退的影响。大鼠每天皮下注射尼古丁两次，持续14天。最后一次注射两周后，大鼠接受线索性或情境性恐惧条件反射训练。训练后24小时和48小时，大鼠分别接受消退训练和消退测试。在训练的所有阶段评估僵住百分比。在线索性任务中，先前的慢性尼古丁处理不影响恐惧反应的获得或训练期间的恐惧消退，但损害了训练期间的恐惧消退。在情境性任务中，相同的尼古丁处理方案不影响恐惧反应的获得或训练期间及训练期间的恐惧消退，但增强了恐惧条件反射的保持。这种先前慢性尼古丁诱导的线索性恐惧消退缺陷和/或对情境的恐惧增强可能是导致从尼古丁依赖发展到焦虑症的关键因素之一。
