Department of Behavioral Science, University of Kentucky College of Medicine, 1110 Veterans Drive, Medical Behavioral Science Building Room 140, Lexington, KY 40536-0086, USA.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD 21224, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2020 Dec 20;103:109974. doi: 10.1016/j.pnpbp.2020.109974. Epub 2020 May 23.
Mechanistic research on behavioral processes underlying substance use disorder might help identify novel targets for interventions development. Drug-related attentional bias and response inhibition deficits have received a great deal of consideration in substance use research, broadly, and cocaine use research, specifically. Studies investigating pharmacological mechanisms that may ameliorate, or further impair, these behaviors relevant to cocaine use are relatively lacking. This study evaluated the impact of acute administration of methylphenidate, a dopamine-favoring reuptake inhibitor, on both gaze-related cocaine-cue-attentional bias and cocaine-cue related disruptions in response inhibition among individuals with cocaine use disorder. Participants (N = 12; 33% female) completed a within-subject, outpatient, acute dosing study. Two sessions were completed in which methylphenidate (60 mg) or placebo were administered followed by completion of an attentional bias task using eye-tracking technology and neutral-cue and cocaine-cue response inhibition tasks. Subjective and physiological effects were also recorded. Significant cocaine cue attentional bias and response inhibition failures were observed during placebo administration. Acute methylphenidate administration reduced cocaine-cue attentional bias as measured by cocaine-cue gaze fixations (d = 1.04; Bayes Factor = 12.37). No statistically significant effects of methylphenidate were observed on response inhibition (Bayes Factors = 0.17-1.04). Methylphenidate produced prototypical subjective and physiological effects. Although the small sample should be considered, these findings indicate acute manipulation of dopaminergic activity reduced cue-related attentional allocation related to cocaine use disorder. Future research evaluating alternative dopaminergic agents and applications within a clinical setting are needed to determine the clinical significance of targeting this neurobehavioral mechanism.
对物质使用障碍相关行为过程的机制研究可能有助于确定干预措施开发的新靶点。药物相关的注意力偏向和反应抑制缺陷在物质使用研究中，广泛地，在可卡因使用研究中，特别是受到了极大的关注。研究调查可能改善或进一步损害与可卡因使用相关的这些行为的药理学机制相对较少。这项研究评估了急性给予哌醋甲酯（一种促进多巴胺再摄取的抑制剂）对可卡因使用障碍患者的注视相关可卡因线索注意力偏向和可卡因线索相关反应抑制中断的影响。参与者（N=12；33%为女性）完成了一项门诊内、急性给药研究。完成了两个疗程，其中给予哌醋甲酯（60mg）或安慰剂，然后使用眼动追踪技术完成注意力偏向任务和中性线索和可卡因线索反应抑制任务。还记录了主观和生理效应。在给予安慰剂时观察到明显的可卡因线索注意力偏向和反应抑制失败。急性哌醋甲酯给药减少了可卡因线索注意力偏向，表现为可卡因线索注视固定（d=1.04；贝叶斯因子=12.37）。在反应抑制方面，没有观察到哌醋甲酯的统计学显著影响（贝叶斯因子=0.17-1.04）。哌醋甲酯产生了典型的主观和生理效应。尽管应考虑到小样本量，但这些发现表明急性操纵多巴胺能活动减少了与可卡因使用障碍相关的线索相关注意力分配。需要评估替代多巴胺能药物并在临床环境中应用的未来研究，以确定针对这种神经行为机制的临床意义。
