Increased Cocaine Motivation Is Associated with Degraded Spatial and Temporal Representations in IL-NAc Neurons
Increased Cocaine Motivation Is Associated with Degraded Spatial and Temporal Representations in IL-NAc Neurons
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DOI：
10.1016/j.neuron.2019.04.015
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发表时间：
2019-07-03
期刊：
影响因子：
16.2
通讯作者：
Witten, Ilana B.
中科院分区：
文献类型：
--
作者：
Cameron, Courtney M.;Murugan, Malavika;Witten, Ilana B.
在戒毒期间，可卡因使用者对可卡因的渴望逐渐增加，导致复吸。从边缘下皮质到核壳的投射（IL-NAc）被认为抑制可卡因寻求。然而，目前尚不清楚IL-NAc神经元是否以及如何有助于与无药期相关的动机增加。我们首先进行细胞分辨率成像的IL-NAc神经元在大鼠在药物寻找测试。这揭示了神经元在可卡因相关背景下具有空间选择性，在寻找可卡因时活动减少，以及寻找可卡因活动与随后的可卡因动机之间呈负相关关系。所有这些特性都因停药期而降低。接下来，我们暂时激活了这个投射，这导致了减少的药物寻求，无论药物戒断期如何。两者合计，这表明，改变IL-NAc活性后，无药期可能会提高可卡因的动机，而不会从根本上改变预测的能力，抑制药物寻求。
Craving for cocaine progressively increases in cocaine users during drug-free periods, contributing to relapse. The projection from the infralimbic cortex to the nucleus accumbens shell (IL-NAc) is thought to inhibit cocaine seeking. However, it is not known whether and how IL-NAc neurons contribute to the increased motivation associated with a drug-free period. We first performed cellular resolution imaging of IL-NAc neurons in rats during a drug-seeking test. This revealed neurons with spatial selectivity within the cocaine-associated context, a decrease in activity around the time of cocaine seeking, and an inverse relationship between cocaine-seeking activity and subsequent cocaine motivation. All these properties were reduced by a drug-free period. Next, we transiently activated this projection, which resulted in reduced drug seeking, regardless of the drug-free period. Taken together, this suggests that altered IL-NAc activity after a drug-free period may enhance cocaine motivation without fundamentally altering the projection's ability to inhibit drug seeking.