Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
J Neurosci. 2010 Jan 6;30(1):276-86. doi: 10.1523/JNEUROSCI.2820-09.2010.
Although neuroadaptations in the nucleus accumbens (NAc) are thought to contribute to nicotine addiction, little is known about the chronic effects of nicotine on NAc neuronal activity. In the present experiment, rats were exposed to a 23 d period of nicotine self-administration (SA), a 30 d abstinence period, and a 7 d period of reexposure to SA. Chronic electrophysiological procedures were used to record the activity of individual NAc neurons on the 3rd and 23rd days of initial SA and on the 1st, 3rd, and 7th days of reexposure. Between-session comparisons showed that NAc neurons exhibit two patterns of plasticity under the present experimental conditions. First, phasic-increase firing patterns time-locked to the nicotine-reinforced lever press do not change during initial SA, but then show increases in prevalence and amplitude after abstinence, which persist during reexposure. Second, for neurons that show no phasic response time-locked to the nicotine-reinforced lever press, average baseline and SA firing rates decrease during initial SA, return to normal during abstinence, and decrease again during reexposure. As a combined consequence of the two types of neurophysiological plasticity, average firing rate of NAc neurons at the time of nicotine-directed behavior undergoes a progressive and persistent net amplification, across the successive stages of SA, abstinence, and reexposure. This net increase in NAc firing at the time of nicotine-directed behavior occurs in association with an increase in animals' motivation to seek nicotine. The adaptations that occur in nicotine-exposed animals do not occur in animals exposed to sucrose. The NAc neurophysiological plasticity potentially contributes to compulsive tobacco use.
尽管人们认为伏隔核（NAc）的神经适应性有助于尼古丁成瘾，但对于尼古丁对 NAc 神经元活动的慢性影响知之甚少。在本实验中，大鼠经历了 23 天的尼古丁自我给药（SA）、30 天的戒断期和 7 天的重新暴露于 SA。使用慢性电生理程序记录了在初始 SA 的第 3 天和第 23 天以及重新暴露的第 1 天、第 3 天和第 7 天单个 NAc 神经元的活动。组间比较表明，在目前的实验条件下，NAc 神经元表现出两种可塑性模式。首先，与尼古丁强化杆按压时间锁定的相位增加放电模式在初始 SA 期间没有变化，但在戒断后会增加发生率和幅度，在重新暴露期间持续增加。其次，对于没有与尼古丁强化杆按压时间锁定的相位反应的神经元，平均基线和 SA 放电率在初始 SA 期间降低，在戒断期间恢复正常，在重新暴露期间再次降低。由于这两种类型的神经生理可塑性的综合结果，NAc 神经元在指向尼古丁的行为时的平均放电率在连续的 SA、戒断和重新暴露阶段经历了渐进和持续的净放大。在指向尼古丁的行为时 NAc 放电的这种净增加与动物寻求尼古丁的动机增加有关。暴露于尼古丁的动物中发生的适应性变化不会发生在暴露于蔗糖的动物中。NAc 的神经生理可塑性可能有助于强迫性吸烟。
