du Hoffmann Johann, Nicola Saleem M
Dominick P. Purpura Department of Neuroscience and.
Dominick P. Purpura Department of Neuroscience and Department of Psychiatry and Behavioral Science, Albert Einstein College of Medicine, New York, New York 10461
J Neurosci. 2014 Oct 22;34(43):14349-64. doi: 10.1523/JNEUROSCI.3492-14.2014.
Approach to reward is a fundamental adaptive behavior, disruption of which is a core symptom of addiction and depression. Nucleus accumbens (NAc) dopamine is required for reward-predictive cues to activate vigorous reward seeking, but the underlying neural mechanism is unknown. Reward-predictive cues elicit both dopamine release in the NAc and excitations and inhibitions in NAc neurons. However, a direct link has not been established between dopamine receptor activation, NAc cue-evoked neuronal activity, and reward-seeking behavior. Here, we use a novel microelectrode array that enables simultaneous recording of neuronal firing and local dopamine receptor antagonist injection. We demonstrate that, in the NAc of rats performing a discriminative stimulus task for sucrose reward, blockade of either D1 or D2 receptors selectively attenuates excitation, but not inhibition, evoked by reward-predictive cues. Furthermore, we establish that this dopamine-dependent signal is necessary for reward-seeking behavior. These results demonstrate a neural mechanism by which NAc dopamine invigorates environmentally cued reward-seeking behavior.
对奖励的趋近是一种基本的适应性行为，其破坏是成瘾和抑郁的核心症状。伏隔核（NAc）多巴胺是奖励预测线索激活强烈奖励寻求行为所必需的，但潜在的神经机制尚不清楚。奖励预测线索会引发NAc中的多巴胺释放以及NAc神经元的兴奋和抑制。然而，多巴胺受体激活、NAc线索诱发的神经元活动和奖励寻求行为之间尚未建立直接联系。在这里，我们使用一种新型微电极阵列，能够同时记录神经元放电和局部多巴胺受体拮抗剂注射。我们证明，在执行蔗糖奖励辨别刺激任务的大鼠的NAc中，阻断D1或D2受体选择性地减弱了奖励预测线索诱发的兴奋，但不影响抑制。此外，我们确定这种多巴胺依赖性信号是奖励寻求行为所必需的。这些结果证明了一种神经机制，通过该机制NAc多巴胺增强了环境线索诱发的奖励寻求行为。
