A Cocaine Context Renews Drug Seeking Preferentially in a Subset of Individuals
A Cocaine Context Renews Drug Seeking Preferentially in a Subset of Individuals
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DOI：
10.1038/npp.2014.131
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发表时间：
2014-11-01
影响因子：
7.6
通讯作者：
Robinson, Terry E.
中科院分区：
文献类型：
--
作者：
Saunders, Benjamin T.;O'Donnell, Elizabeth G.;Robinson, Terry E.
成瘾的特点是高复发倾向，部分原因是与药物相关的线索可以获得巴甫洛夫激励动机属性，并且作为激励刺激，这些线索可以煽动和激发寻求药物的行为。然而，在将激励显著性归因于奖励线索的倾向上，存在相当大的个体差异。在一些大鼠（“符号追踪者”，st）中，离散和可定位的奖励线索比其他大鼠（“目标追踪者”，gt）更有效。我们询问是否存在与可卡因相关的情境线索的类似个体差异。可卡因情境条件动机以两种方式量化：(1)可卡因情境引起条件性多动的能力；(2)先前自我使用可卡因的情境重新产生可卡因寻求行为的能力。最后，我们评估了伏隔核内氟苯酚（一种非选择性多巴胺受体拮抗剂）对环境更新的影响。与使用离散线索的研究相比，可卡因环境刺激了更大的条件性多动，并且在GTs中比STs更强烈地重新激活了已熄灭的可卡因寻求。此外，可卡因环境的更新被伏隔核多巴胺受体的拮抗所阻断。因此，在不同个体中，与可卡因相关的情境线索比离散线索更容易获得对行为的动机控制，在这些个体中，可卡因情境创造可卡因条件动机的能力需要伏隔核核心的多巴胺。我们推测，不同的个体可能对不同的复发“触发因素”有优先敏感性。
Addiction is characterized by a high propensity for relapse, in part because cues associated with drugs can acquire Pavlovian incentive motivational properties, and acting as incentive stimuli, such cues can instigate and invigorate drug-seeking behavior. There is, however, considerable individual variation in the propensity to attribute incentive salience to reward cues. Discrete and localizable reward cues act as much more effective incentive stimuli in some rats ('sign-trackers', STs), than others ('goal-trackers', GTs). We asked whether similar individual variation exists for contextual cues associated with cocaine. Cocaine context conditioned motivation was quantified in two ways: (1) the ability of a cocaine context to evoke conditioned hyperactivity and (2) the ability of a context in which cocaine was previously self-administered to renew cocaine-seeking behavior. Finally, we assessed the effects of intra-accumbens core flupenthixol, a nonselective dopamine receptor antagonist, on context renewal. In contrast to studies using discrete cues, a cocaine context spurred greater conditioned hyperactivity, and more robustly renewed extinguished cocaine seeking in GTs than STs. In addition, cocaine context renewal was blocked by antagonism of dopamine receptors in the accumbens core. Thus, contextual cues associated with cocaine preferentially acquire motivational control over behavior in different individuals than do discrete cues, and in these individuals the ability of a cocaine context to create conditioned motivation for cocaine requires dopamine in the core of the nucleus accumbens. We speculate that different individuals may be preferentially sensitive to different 'triggers' of relapse.