Chemogenetic Activation of an Extinction Neural Circuit Reduces Cue-Induced Reinstatement of Cocaine Seeking
Chemogenetic Activation of an Extinction Neural Circuit Reduces Cue-Induced Reinstatement of Cocaine Seeking
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DOI：
10.1523/jneurosci.0773-16.2016
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发表时间：
2016-09-28
影响因子：
5.3
通讯作者：
Peters, Jamie
中科院分区：
文献类型：
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作者：
Augur, Isabel F.;Wyckoff, Andrew R.;Peters, Jamie
腹内侧前额叶皮层 (vmPFC) 已被证明对可卡因寻求行为具有负调节作用，但利用 vmPFC 活性来减少可卡因复吸的确切条件目前尚不清楚。我们使用病毒介导的设计受体基因转移 (DREADD) 来激活 vmPFC 神经元，并在大鼠自我给药复发模型中检查对可卡因寻求的影响。 Gq-DREADD 激活 vmPFC 神经元减少了由可卡因相关线索引起的可卡因寻求的恢复，但不是由可卡因本身引起的。我们使用逆向 DREADD 方法将 Gq-DREADD 限制在 vmPFC 神经元上，这些神经元投射到内侧伏隔核壳，证实这些神经元是线索诱导的可卡因寻找恢复减少的原因。 vmPFC 激活对提示诱导恢复的影响取决于先前的消退训练，与报道的该结构在消退记忆中的作用一致。这些数据有助于定义可以利用灭绝神经回路的化学遗传学激活来减少由提醒线索触发的复发的条件。
The ventromedial prefrontal cortex (vmPFC) has been shown to negatively regulate cocaine-seeking behavior, but the precise conditions by which vmPFC activity can be exploited to reduce cocaine relapse are currently unknown. We used viral-mediated gene transfer of designer receptors (DREADDs) to activate vmPFC neurons and examine the consequences on cocaine seeking in a rat self-administration model of relapse. Activation of vmPFC neurons with the Gq-DREADD reduced reinstatement of cocaine seeking elicited by cocaine-associated cues, but not by cocaine itself. We used a retro-DREADD approach to confine the Gq-DREADD to vmPFC neurons that project to the medial nucleus accumbens shell, confirming that these neurons are responsible for the decreased cue-induced reinstatement of cocaine seeking. The effects of vmPFC activation on cue-induced reinstatement depended on prior extinction training, consistent with the reported role of this structure in extinction memory. These data help define the conditions under which chemogenetic activation of extinction neural circuits can be exploited to reduce relapse triggered by reminder cues.