Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany.
Department of Molecular Biology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Psychopharmacology (Berl). 2021 Aug;238(8):2335-2346. doi: 10.1007/s00213-021-05858-z. Epub 2021 May 5.
In classical conditioning, sign-tracking reflects behavior directed toward a conditioned stimulus (CS) in expectation of a reward (unconditioned stimulus, US); in contrast, goal-tracking describes behavior directed toward the location of delivery of a US. As cues previously paired with drugs of abuse promote drug-seeking and drug-taking behavior in both animals and humans and thus contribute to the severity of substance abuse, sign-tracking may represent a maladaptive cue-focused behavior that may increase addiction vulnerability as compared to goal-tracking. Recent studies do, in fact, support this possibility. Previous work in this area has focused primarily on paradigms using relatively limited exposure to drug rather than extended drug intake.
Here, we used the DSM-IV-based 3-criteria (3-CRIT) model and examined whether a relationship exists between sign- or goal-tracking phenotypes and the prevalence of criteria associated with addiction-like behavior following extended cocaine self-administration as measured in this model.
Forty-six male Sprague Dawley rats underwent a Pavlovian conditioned approach (PCA) procedure and were characterized along a continuum as goal-trackers (GTs), intermediates (INTs), or sign-trackers (STs). The animals were subsequently trained to intravenous self-administer cocaine during 45 self-administration (SA) sessions and characterized for the 3 criteria outlined in the model: persistence of drug-seeking, motivation for cocaine-taking, and resistance to punishment.
We performed correlational analyses on the traits measured, finding no relationships between PCA score and addiction-like characteristics measured using the 3-CRIT model of addiction. However, STs showed significantly greater resistance to punishment than GTs.
Phenotyping along a continuum of PCA scores may not be a valid predictor for identifying vulnerability to the addiction-like behaviors examined using the 3-CRIT model. However, PCA phenotype may predict a single feature of the 3-CRIT model, resistance to punishment, among those rats classified as either STs or GTs.
在经典条件反射中,标记跟踪反映了行为指向条件刺激(CS),以期望获得奖励(非条件刺激,US);相比之下,目标跟踪描述了指向 US 传递位置的行为。由于先前与滥用药物配对的线索在动物和人类中都促进了觅药和用药行为,从而导致了物质滥用的严重程度,因此,标记跟踪可能代表一种适应不良的、以线索为中心的行为,与目标跟踪相比,可能会增加成瘾易感性。事实上,最近的研究确实支持了这种可能性。该领域的先前工作主要集中在使用相对有限的药物暴露而非延长药物摄入的范式上。
在这里,我们使用基于 DSM-IV 的 3 标准(3-CRIT)模型,并检查了标记或目标跟踪表型与以下模型中测量的延长可卡因自我给药后与成瘾样行为相关的标准的流行之间是否存在关系。
46 只雄性 Sprague Dawley 大鼠接受了一种条件性趋近(PCA)程序,并沿着一个连续体被描绘为目标跟踪者(GTs)、中间(INTs)或标记跟踪者(STs)。随后,这些动物接受了 45 次静脉内自我给药(SA)训练,并对该模型中概述的 3 个标准进行了特征描述:觅药的持续存在、可卡因摄取的动机以及对惩罚的抵抗力。
我们对所测量的特征进行了相关分析,发现 PCA 评分与使用成瘾 3-CRIT 模型测量的成瘾样特征之间没有关系。然而,STs 显示出比 GTs 更强的抗惩罚能力。
沿着 PCA 评分连续体进行表型分析可能不是识别使用 3-CRIT 模型检查的成瘾样行为易感性的有效预测因子。然而,PCA 表型可能预测 3-CRIT 模型中单一特征,即在被归类为 STs 或 GTs 的大鼠中,抗惩罚能力。