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首页> 美国卫生研究院文献>The Journal of Neuroscience >Diverse Roads to Relapse: A Discriminative Cue Signaling Cocaine Availability Is More Effective in Renewing Cocaine Seeking in Goal Trackers Than Sign Trackers and Depends on Basal Forebrain Cholinergic Activity
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Diverse Roads to Relapse: A Discriminative Cue Signaling Cocaine Availability Is More Effective in Renewing Cocaine Seeking in Goal Trackers Than Sign Trackers and Depends on Basal Forebrain Cholinergic Activity

机译：多样的复发之路：区分信号提示可卡因的可利用性比起符号跟踪器更有效地更新可卡因在目标追踪器中的寻找并依赖于基础前脑胆碱能活动

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Stimuli associated with taking drugs are notorious instigators of relapse. There is, however, considerable variation in the motivational properties of such stimuli, both as a function of the individual and the nature of the stimulus. The behavior of some individuals (sign trackers, STs) is especially influenced by cues paired with reward delivery, perhaps because they are prone to process information via dopamine-dependent, cue-driven, incentive salience systems. Other individuals (goal trackers, GTs) are better able to incorporate higher-order contextual information, perhaps because of better executive/attentional control over behavior, which requires frontal cortical cholinergic activity. We hypothesized, therefore, that a cue that “sets the occasion” for drug taking (a discriminative stimulus, DS) would reinstate cocaine seeking more readily in GTs than STs and that this would require intact cholinergic neurotransmission. To test this, male STs and GTs were trained to self-administer cocaine using an intermittent access schedule with periods of cocaine availability and unavailability signaled by a DS+ and a DS−, respectively. Thereafter, half of the rats received an immunotoxic lesion that destroyed 40–50% of basal forebrain cholinergic neurons and later, after extinction training, were tested for the ability of noncontingent presentations of the DS+ to reinstate cocaine seeking behavior. The DS+ was much more effective in reinstating cocaine seeking in GTs than STs and this effect was abolished by cholinergic losses despite the fact that all rats continued to orient to the DS+. We conclude that vulnerability to relapse involves interactions between individual cognitive–motivational biases and the form of the drug cue encountered.>SIGNIFICANCE STATEMENT The most predictable outcome of a diagnosis of addiction is a high chance for relapse. When addicts encounter cues previously associated with drug, their attention may be unduly attracted to such cues and these cues can evoke motivational states that instigate and maintain drug-seeking behavior. Although sign-tracking rats were previously demonstrated to exhibit greater relapse vulnerability to Pavlovian drug cues paired with drug delivery, here, we demonstrate that their counterparts, the goal trackers, are more vulnerable if the drug cue acts to signal drug availability and that the forebrain cholinergic system mediates such vulnerability. Given the importance of contextual cues for triggering relapse and the human cognitive–cholinergic capacity for the processing of such cues, goal trackers model essential aspects of relapse vulnerability.
机译：与吸毒有关的刺激是臭名昭著的复发诱因。但是，这种刺激的动机特性在很大程度上取决于个人和刺激的性质。某些线索（符号跟踪器，ST）的行为尤其受提示与奖励传递配对的影响，这可能是因为他们倾向于通过依赖于多巴胺，提示驱动的激励显着系统来处理信息。其他人（目标跟踪器，GT）能够更好地合并高阶上下文信息，这可能是因为对行为的更好的执行/注意控制，这需要额叶皮质胆碱能活动。因此，我们假设，一个提示“为吸毒提供了时机”（歧视性刺激DS）将恢复可卡因在GT中比ST更加容易地寻求可卡因，这将需要完整的胆碱能神经传递。为了测试这一点，对男性ST和GT进行了训练，使其使用间歇性访问时间表自我管理可卡因，并通过DS + 和DS -发出可卡因可用和不可用的时段， 分别。此后，一半的大鼠受到免疫毒性损害，该损害破坏了40-50％的基底前脑胆碱能神经元，随后在消光训练后测试了DS + 的非偶然性恢复可卡因的能力寻求行为。 DS + 在恢复GTs中的可卡因寻找方面比STs有效得多，尽管所有大鼠都继续向DS + 定向，但胆碱能丧失消除了这种作用。 。我们得出结论，复发易感性涉及个体认知动机偏见与所遇到的药物提示形式之间的相互作用。>显着性声明：成瘾诊断的最可预测的结果是复发的可能性很高。当吸毒者遇到以前与毒品有关的线索时，他们的注意力可能会被这种线索过度吸引，而这些线索会唤起激发和维持寻求毒品行为的动机状态。尽管以前已经证明符号跟踪大鼠对帕夫洛夫药物提示和药物输送表现出更大的复发易感性，但在这里，我们证明了如果药物提示起到信号指示药物可及性和前脑的作用，则其对应的目标追踪者会更脆弱。胆碱能系统介导了这种脆弱性。鉴于情境提示对于触发复发的重要性以及人类认知-胆碱能治疗此类提示的能力，目标跟踪器可为复发易感性的重要方面建模。

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