Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Biol Psychiatry. 2010 Apr 15;67(8):737-44. doi: 10.1016/j.biopsych.2009.11.006. Epub 2009 Dec 30.
Dopamine signaling in the nucleus accumbens (NAc) is essential for goal-directed behaviors and primarily arises from burst firing of ventral tegmental area neurons. However, the role of associative neural substrates such as the basolateral amygdala (BLA) in regulating phasic dopamine release in the NAc, particularly during reward seeking, remains unknown.
Male Sprague-Dawley rats learned to discriminate two cues: a discriminative stimulus (DS) that predicted sucrose reinforcement contingent upon a lever press and a nonassociated stimulus (NS) that predicted a second lever never reinforced with sucrose. Following training, a test session was completed in which NAc dopamine was measured using fast-scan cyclic voltammetry in conjunction with inactivation of the ipsilateral BLA (gamma-aminobutyric acid agonists; baclofen/muscimol) to determine the contribution of BLA activity to dopamine release in the NAc core during the task.
Under vehicle conditions, DS and NS presentation elicited dopamine release within the NAc core. The DS evoked significantly more dopamine than the NS. Inactivation of the BLA selectively attenuated the magnitude of DS-evoked dopamine release, concurrent with an attenuation of DS-evoked conditioned approaches. Other behavioral responses (e.g., lever pressing) and dopamine release concomitant with those events were unaltered by BLA inactivation. Furthermore, neither ventral tegmental area electrically stimulated dopamine release nor the probability of high concentration dopamine release events was altered following BLA inactivation.
These results demonstrate that the BLA terminally modulates dopamine signals within the NAc core under specific, behaviorally relevant conditions, illustrating a functional mechanism by which the BLA selectively facilitates responding to motivationally salient environmental stimuli.
伏隔核(NAc)中的多巴胺信号对于目标导向行为至关重要,主要源于腹侧被盖区神经元的爆发式放电。然而,在调节 NAc 中多巴胺的相位释放方面,包括在奖励寻求过程中,诸如基底外侧杏仁核(BLA)等关联神经基质的作用仍然未知。
雄性 Sprague-Dawley 大鼠学会区分两种线索:一个是条件性刺激(DS),它预测蔗糖强化取决于压杆;另一个是非条件性刺激(NS),它预测第二个杆从未与蔗糖强化相关联。在训练后,完成了一个测试阶段,使用快速扫描循环伏安法测量 NAc 中的多巴胺,同时对同侧 BLA 进行失活(γ-氨基丁酸激动剂;巴氯芬/毒蕈碱),以确定 BLA 活性对任务期间 NAc 核心中多巴胺释放的贡献。
在载体条件下,DS 和 NS 的呈现引起了 NAc 核心中的多巴胺释放。DS 诱发的多巴胺释放显著多于 NS。BLA 的失活选择性地减弱了 DS 诱发的多巴胺释放的幅度,同时减弱了 DS 诱发的条件性接近。BLA 失活对其他行为反应(例如压杆)和伴随这些事件的多巴胺释放没有影响。此外,BLA 失活后,腹侧被盖区电刺激多巴胺释放或高浓度多巴胺释放事件的概率没有改变。
这些结果表明,在特定的、与行为相关的条件下,BLA 终末调节 NAc 核心中的多巴胺信号,说明了 BLA 选择性促进对动机相关环境刺激反应的功能机制。