Orexin-1 receptor signaling increases motivation for cocaine-associated cues.
Orexin-1 receptor signaling increases motivation for cocaine-associated cues.
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DOI：
10.1111/ejn.12866
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发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Aston-Jones G
中科院分区：
文献类型：
--
作者：
Bentzley BS;Aston-Jones G
食欲素/下丘脑泌素系统参与多个可卡因成瘾过程，这些过程涉及与药物相关的环境线索，包括线索诱导的已消退的可卡因寻求行为的复燃以及条件性位置偏爱表达。然而，食欲素系统在一些较少依赖线索的行为中不起作用，比如可卡因激发的已消退的可卡因寻求行为的复燃以及低努力程度的可卡因自我给药。我们假设与可卡因相关的线索（而非单独的可卡因）会激活食欲素1型受体（OX1R）的信号传导，并且这种由线索激活的OX1R信号传导会增加对可卡因的动机。在给予OX1R拮抗剂SB - 334867（SB）或赋形剂预处理后，通过行为 - 经济需求曲线分析，在有或无光 + 声音线索的情况下，对斯普拉格 - 道利大鼠的可卡因动机进行测量。当存在与可卡因相关的线索时，对可卡因的需求更高，并且SB仅在存在这些线索的情况下降低可卡因需求。然后我们探究可卡因需求是否与线索诱导的可卡因寻求行为的复燃相关，因为这两个过程都部分地由以食欲素依赖方式的与可卡因相关的线索所驱动。SB阻断了线索诱导的复燃行为，并且基线需求预测了SB的功效，在高需求动物（即具有最强线索依赖行为的动物）中效果最大。我们得出结论，OX1R信号传导增加了与可卡因相关线索的强化效力，但对单独的可卡因没有作用。这支持了我们的观点，即食欲素在条件性线索激活动机反应的能力中起着重要作用。
The orexin/hypocretin system is involved in multiple cocaine addiction processes that involve drug-associated environmental cues, including cue-induced reinstatement of extinguished cocaine seeking and expression of conditioned place preference. However, the orexin system does not play a role in several behaviors that are less cue-dependent, such as cocaine-primed reinstatement of extinguished cocaine seeking and low-effort cocaine self-administration. We hypothesized that cocaine-associated cues, but not cocaine alone, engage signaling at orexin-1 receptors (OX1R), and this cue-engaged OX1R signaling increases motivation for cocaine. Motivation for cocaine was measured in Sprague-Dawley rats with behavioral-economic demand curve analysis after pretreatment with the OX1R antagonist SB-334867 (SB) or vehicle with and without light+tone cues. Demand for cocaine was higher when cocaine-associated cues were present, and SB only reduced cocaine demand in the presence of these cues. We then asked if cocaine demand is linked to cued-reinstatement of cocaine seeking, as both procedures are partially driven by cocaine-associated cues in an orexin-dependent manner. SB blocked cue-induced reinstatement behavior, and baseline demand predicted SB efficacy with the largest effect in high demand animals, i.e., animals with the greatest cue-dependent behavior. We conclude that OX1R signaling increases the reinforcing efficacy of cocaine-associated cues but not for cocaine alone. This supports our view that orexin plays a prominent role in the ability of conditioned cues to activate motivational responses.
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影响因子：
--
作者：
Mahler, Stephen V.;Smith, Rachel J.;Moorman, David E.;Sartor, Gregory C.;Aston-Jones, Gary
通讯作者：
Aston-Jones, Gary
影响因子：
4.7
作者：
Smith RJ;Tahsili-Fahadan P;Aston-Jones G
通讯作者：
Aston-Jones G
DOI：
10.1111/j.1460-9568.2009.06844.x
发表时间：
2009-08
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Smith RJ;See RE;Aston-Jones G
通讯作者：
Aston-Jones G
影响因子：
3.4
作者：
Mahler, Stephen V.;Smith, Rachel J.;Aston-Jones, Gary
通讯作者：
Aston-Jones, Gary
影响因子：
2.7
作者：
Porter, RA;Chan, WN;Austin, N
通讯作者：
Austin, N