Fox Helen C, Jackson Eric D, Sinha Rajita
Yale Stress Center, Department of Psychiatry, Yale University School of Medicine, 2 Church Street South, Suite 209, Room 209Q, New Haven, CT 06519, USA.
Psychoneuroendocrinology. 2009 Sep;34(8):1198-207. doi: 10.1016/j.psyneuen.2009.03.007. Epub 2009 Apr 16.
Cocaine dependence is characterized by stress system dysregulation, including elevated cortisol activity, emotional negativity, and behavioral disinhibition. High levels of stress and glucocorticoids are also known to affect learning, memory and executive function. Therefore, we examined the relationships between chronic cocaine use, elevated distress and learning and memory dysfunction in abstinent cocaine dependent (CD) individuals, and whether these measures were associated with cocaine relapse outcomes.
Stress was assessed in 36 inpatient treatment engaged CD individuals and 36 demographically matched healthy control (HC) participants using the Perceived Stress Scale (PSS) and repeated morning salivary cortisol levels over three consecutive days. The Rey Auditory Verbal Learning Test (RAVLT) was conducted to measure verbal learning, memory, and executive function. Prospective assessment of cocaine use outcomes during 90 days following discharge from inpatient treatment was also conducted.
CD patients showed higher levels of distress compared to controls in PSS scores and cortisol levels. They also demonstrated a significantly reduced learning curve, and fewer correct responses and more errors on recognition. Elevated cortisol was significantly associated with worse RAVLT performance in CD patients. Poor memory scores, but not distress measures, were significantly associated with greater cocaine use after inpatient treatment.
These findings are the first to demonstrate that learning and memory deficits in CD individuals are associated with enhanced cortisol and with cocaine use outcomes after inpatient treatment. The findings are consistent with recent addiction models suggesting that chronic cocaine-related neuroadaptations affects learning and memory function, which in turn, influences drug use outcomes.
可卡因依赖的特征是应激系统失调,包括皮质醇活性升高、情绪消极和行为抑制。高水平的应激和糖皮质激素也已知会影响学习、记忆和执行功能。因此,我们研究了长期使用可卡因的戒断可卡因依赖(CD)个体中,高应激与学习和记忆功能障碍之间的关系,以及这些指标是否与可卡因复发结果相关。
使用感知应激量表(PSS)对36名接受住院治疗的CD个体和36名人口统计学匹配的健康对照(HC)参与者进行应激评估,并连续三天重复测量早晨唾液皮质醇水平。进行雷伊听觉词语学习测验(RAVLT)以测量言语学习、记忆和执行功能。还对住院治疗出院后90天内的可卡因使用结果进行了前瞻性评估。
与对照组相比,CD患者在PSS评分和皮质醇水平上表现出更高的应激水平。他们还表现出学习曲线显著降低,识别时正确反应更少且错误更多。皮质醇升高与CD患者较差的RAVLT表现显著相关。记忆分数差,但不是应激指标,与住院治疗后更多的可卡因使用显著相关。
这些发现首次表明,CD个体的学习和记忆缺陷与皮质醇升高以及住院治疗后的可卡因使用结果相关。这些发现与最近的成瘾模型一致,表明慢性可卡因相关的神经适应性变化会影响学习和记忆功能,进而影响药物使用结果。