Saunders Benjamin T, O'Donnell Elizabeth G, Aurbach Elyse L, Robinson Terry E
1] Department of Psychology (Biopsychology Program), University of Michigan, Ann Arbor, MI, USA [2] Center for Integrative Neuroscience, University of California-San Francisco, San Francisco, CA, USA [3] Ernest Gallo Clinic and Research Center, University of California-San Francisco, San Francisco, CA, USA.
Department of Psychology (Biopsychology Program), University of Michigan, Ann Arbor, MI, USA.
Neuropsychopharmacology. 2014 Nov;39(12):2816-23. doi: 10.1038/npp.2014.131. Epub 2014 Jun 4.
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.
成瘾的特点是复发倾向高,部分原因是与药物相关的线索可获得巴甫洛夫式的激励动机属性,并且作为激励刺激,这些线索可激发并增强觅药行为。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。离散且可定位的奖励线索在一些大鼠(“信号追踪者”,STs)中比其他大鼠(“目标追踪者”,GTs)更有效地充当激励刺激。我们询问与可卡因相关的情境线索是否存在类似的个体差异。可卡因情境条件性动机通过两种方式进行量化:(1)可卡因情境引发条件性多动的能力,以及(2)先前自我给药可卡因的情境恢复觅药行为的能力。最后,我们评估了伏隔核核心内注射氟哌噻吨(一种非选择性多巴胺受体拮抗剂)对情境恢复的影响。与使用离散线索的研究不同,可卡因情境在GTs中比STs引发更大的条件性多动,并更有力地恢复消退的可卡因觅药行为。此外,伏隔核核心中多巴胺受体的拮抗作用阻断了可卡因情境恢复。因此,与可卡因相关的情境线索在不同个体中比离散线索更优先地获得对行为的动机控制,并且在这些个体中,可卡因情境为可卡因创造条件性动机的能力需要伏隔核核心中的多巴胺。我们推测不同个体可能对复发的不同“触发因素”有不同的敏感性。