ΔFosB in the nucleus accumbens regulates food-reinforced instrumental behavior and motivation
ΔFosB in the nucleus accumbens regulates food-reinforced instrumental behavior and motivation
复制标题
DOI：
10.1523/jneurosci.1124-06.2006
复制
发表时间：
2006-09-06
影响因子：
5.3
通讯作者：
Taylor, Jane R.
中科院分区：
文献类型：
--
作者：
Olausson, Peter;Jentsch, J. David;Taylor, Jane R.
动机的改变与一些精神疾病的病理生理学有关，包括药物滥用和抑郁症。已知反复暴露于药物滥用或压力下会持续诱导伏隔核（NAc）和背纹状体中的转录因子δ FosB，这种效应被假设有助于多巴胺调节信号的神经适应。然而，对于Delta FosB在食欲动机行为失调中的具体作用，我们知之甚少。通过病毒介导的基因转移，我们在双转基因小鼠的NAc和背纹状体中，特别是在大鼠的NAc核心中，诱导了δ FosB的过表达，增强了食物增强的工具性能和渐进式比率反应。在大鼠反复接触可卡因、安非他命、MDMA[(+)-3,4-亚甲基二氧基甲基苯丙胺]或尼古丁后，发现了非常相似的行为影响。这些结果揭示了Delta FosB对动机过程的强大调节作用，并提供了通过诱导NAc核心内Delta FosB引起的药物诱导基因表达改变可能在动机影响对工具行为的影响中发挥关键作用的证据。
Alterations in motivation have been implicated in the pathophysiology of several psychiatric disorders, including substance abuse and depression. Repeated exposure to drugs of abuse or stress is known to persistently induce the transcription factor Delta FosB in the nucleus accumbens (NAc) and dorsal striatum, effects hypothesized to contribute to neuroadaptations in dopamine-regulated signaling. Little is known, however, about the specific involvement of Delta FosB in dysregulation of appetitively motivated behaviors. We show here that inducible overexpression of Delta FosB in NAc and dorsal striatum of bitransgenic mice, or specifically in the NAc core of rats by use of viral-mediated gene transfer, enhanced food-reinforced instrumental performance and progressive ratio responding. Very similar behavioral effects were found after previous repeated exposure to cocaine, amphetamine, MDMA [(+)-3,4-methylenedioxymethamphetamine], or nicotine in rats. These results reveal the powerful regulation of motivational processes by Delta FosB, and provide evidence that drug-induced alterations in gene expression via induction of Delta FosB within the NAc core may play a critical role in the impact of motivational influences on instrumental behavior.