Abstract

Endogenous opioids regulate pain, drug reward, and stress responses. We have previously shown reduced hypothalamic-pituitary-adrenal (HPA) responses to psychological stress and to opioid blockade among dependent smokers. In this study, we examined the extent to which biologically confirmed nicotine withdrawal alters endogenous opioid regulation of HPA axis functioning during rest and in response to acute stress. Smokers were randomly assigned to one of two conditions; 24 h withdrawal from all nicotine-containing products (n = 62) or smoking ad libitum (n = 44). A nonsmoking comparison group (n = 43) was also included. Participants (85 males and 64 females) completed two acute stress sessions during which a placebo or 50 mg of naltrexone (opioid antagonist) were administered using a double-blind design. Blood and saliva samples (assayed for cortisol and adrenocorticotropic hormone, i.e. ACTH) and mood measures were obtained during a resting absorption period, after acute stress (public speaking, mental arithmetic, and cold pressor tasks), and during an extended recovery period. Results indicated that opioid blockade (naltrexone) was associated with increased ACTH and cortisol responses to stress, and tobacco withdrawal was associated with blunted hormonal responses. A pattern of sex differences also emerged, with women exhibiting reduced ACTH responses to stress and higher ACTH and plasma cortisol responses to opioid blockade. These results indicated that compared to ad libitum smoking, nicotine withdrawal is associated with blunted opioid modulation of the HPA axis. Sex may modulate these effects. Blunted endogenous opioid regulation may underlie an incentive process that reinforces smoking behavior and may warrant therapeutic attention.

摘要

内源性阿片类药物可调节疼痛、药物奖励和压力反应。我们之前已经表明，依赖吸烟者对心理压力和阿片类药物阻断的下丘脑-垂体-肾上腺 (HPA) 反应减少。在这项研究中，我们检查了生物学证实的尼古丁戒断在多大程度上改变了内源性阿片类药物对 HPA 轴功能在休息期间和对急性压力的反应的调节。吸烟者被随机分配到两种情况之一；24 小时戒断所有含尼古丁产品（n  = 62）或随意吸烟（n  = 44）。非吸烟对照组（n = 43) 也包括在内。参与者（85 名男性和 64 名女性）完成了两次急性压力训练，期间使用双盲设计给予安慰剂或 50mg 纳曲酮（阿片类药物拮抗剂）。在静息吸收期间、急性压力（公开演讲、心算和冷加压任务）之后以及在延长的恢复期间获得血液和唾液样本（测定皮质醇和促肾上腺皮质激素，即 ACTH）和情绪测量值。结果表明，阿片类药物阻滞剂（纳曲酮）与促肾上腺皮质激素和皮质醇对压力的反应增加有关，而戒烟与激素反应减弱有关。还出现了一种性别差异模式，女性对压力的 ACTH 反应降低，而对阿片类药物阻断的 ACTH 和血浆皮质醇反应升高。这些结果表明，与随意吸烟相比，尼古丁戒断与 HPA 轴的阿片类药物调节减弱有关。性可以调节这些影响。减弱的内源性阿片类药物调节可能是强化吸烟行为的激励过程的基础，并且可能需要治疗关注。