Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France.
PLoS One. 2011;6(9):e24049. doi: 10.1371/journal.pone.0024049. Epub 2011 Sep 22.
Nicotine self-administration (SA) is maintained by several variables, including the reinforcing properties of nicotine-paired cues and the nicotine-induced amplification of those cue properties. The nucleus accumbens (NAc) is implicated in mediating the influence of these variables, though the underlying neurophysiological mechanisms are not yet understood. In the present study, Long-Evans rats were trained to self-administer nicotine. During SA sessions each press of a lever was followed by an intravenous infusion of nicotine (30 µg/kg) paired with a combined light-tone cue. Extracellular recordings of single-neuron activity showed that 20% of neurons exhibited a phasic change in firing during the nicotine-directed operant, the light-tone cue, or both. The phasic change in firing for 98% of neurons was an increase. Sixty-two percent of NAc neurons additionally or alternatively showed a sustained decrease in average firing during the SA session relative to a presession baseline period. These session decreases in firing were significantly less prevalent in a group of neurons that were activated during either the operant or the cue than in a group of neurons that were nonresponsive during those events (referred to as task-activated and task-nonactivated neurons, respectively). Moreover, the session decrease in firing was dose-dependent for only the task-nonactivated neurons. The data of the present investigation provide supportive correlational evidence for two hypotheses: (1) excitatory neurophysiological mechanisms mediate the NAc role in cue-maintenance of nicotine SA, and (2) a differential nicotine-induced inhibition of task-activated and task-nonactivated neurons mediates the NAc role in nicotine-induced amplification of cue effects on nicotine SA.
尼古丁自我给药（SA）由多种变量维持，包括尼古丁配对线索的强化特性和尼古丁诱导的这些线索特性的放大。伏隔核（NAc）被认为介导了这些变量的影响，尽管其潜在的神经生理机制尚不清楚。在本研究中，长爪沙鼠被训练进行尼古丁自我给药。在 SA 期间，每次按压杠杆都会伴随着静脉内输注尼古丁（30µg/kg），并与光-音线索配对。单细胞活动的细胞外记录显示，20%的神经元在尼古丁定向操作性、光-音线索或两者的作用下表现出冲动性放电变化。98%的神经元的冲动性放电变化是增加。62%的 NAc 神经元在 SA 期间与基线期相比，平均放电持续减少。与在这些事件中激活的神经元组相比，在这些事件中无反应的神经元组（分别称为操作性神经元和线索神经元）中，这种放电减少在群体中显著不常见。此外，仅对非操作性神经元，放电减少与剂量呈依赖性。本研究的结果提供了支持两种假说的相关性证据：（1）兴奋性神经生理机制介导了 NAc 在维持尼古丁 SA 的线索中的作用；（2）尼古丁诱导的对操作性神经元和线索神经元的抑制作用不同，介导了 NAc 在尼古丁诱导的线索对尼古丁 SA 的影响放大中的作用。
