Milivojevic Verica, Fox Helen C, Jayaram-Lindstrom Nitya, Hermes Gretchen, Sinha Rajita
The Yale Stress Center, Yale University School of Medicine, Department of Psychiatry 2 Church Street South, Suite 209, New Haven, CT, 06519, USA.
Stony Brook University, Health Sciences Center, T10-040B, Stony Brook, NY, 11794, USA.
Drug Alcohol Depend. 2017 Oct 1;179:275-279. doi: 10.1016/j.drugalcdep.2017.07.017. Epub 2017 Aug 10.
Chronic drug abuse leads to sex-specific changes in drug cue and stress physiologic and neuroendocrine reactivity as well as in neural responses to stress and cue-related challenges and in executive function such as inhibitory control, cognitive flexibility and self control. Importantly, these functions have been associated with high risk of relapse and treatment. Alpha-2 agonism may enhance inhibitory cognitive processes in the face of stress with sex-specific effects, however this has not been previously assessed in cocaine dependence.
Forty inpatient treatment-seeking cocaine dependent individuals (13F/27M) were randomly assigned to receive either placebo or up to 3mgs of Guanfacine. Three laboratory sessions were conducted following 3-4 weeks of abstinence, where patients were exposed to three 10-min personalized guided imagery conditions (stress, drug cue, combined stress/cue), one per day, on consecutive days in a random, counterbalanced order. The Stroop task was administered at baseline and immediately following imagery exposure.
Guanfacine treated women improved their performance on the Stroop task following exposure to all 3 imagery conditions compared with placebo women (p=0.02). This improvement in cognitive inhibitory performance was not observed in the men.
Enhancing the ability to cognitively regulate in the face of stress, drug cues and combined stress and drug cue reactivity may be key targets for medications development in cocaine dependent women.
长期药物滥用会导致药物线索和应激生理及神经内分泌反应性出现性别特异性变化，以及对压力和线索相关挑战的神经反应和执行功能（如抑制控制、认知灵活性和自我控制）出现变化。重要的是，这些功能与高复发风险和治疗相关。α-2激动作用可能会增强面对压力时的抑制性认知过程，并产生性别特异性影响，然而此前尚未在可卡因依赖中对此进行评估。
40名寻求住院治疗的可卡因依赖个体（13名女性/27名男性）被随机分配接受安慰剂或高达3毫克的胍法辛治疗。在禁欲3 - 4周后进行三次实验室测试，患者在连续三天以随机、平衡的顺序每天接受一种10分钟的个性化引导意象条件（压力、药物线索、压力/线索组合）。在基线和意象暴露后立即进行Stroop任务测试。
与接受安慰剂的女性相比，接受胍法辛治疗的女性在暴露于所有三种意象条件后，其在Stroop任务中的表现有所改善（p = 0.02）。男性未观察到这种认知抑制表现的改善。
增强面对压力、药物线索以及压力与药物线索组合时的认知调节能力，可能是可卡因依赖女性药物研发的关键靶点。
