Effects of Prazosin on Provoked Alcohol Craving and Autonomic and Neuroendocrine Response to Stress in Alcohol Use Disorder.
Effects of Prazosin on Provoked Alcohol Craving and Autonomic and Neuroendocrine Response to Stress in Alcohol Use Disorder.
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DOI：
10.1111/acer.14378
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
Fox HC
中科院分区：
文献类型：
--
作者：
Milivojevic V;Angarita GA;Hermes G;Sinha R;Fox HC
慢性酒精导致应激生物学和自主神经觉醒的变化，导致急性酒精戒断症状、下丘脑-垂体-肾上腺（HPA）轴反应的神经内分泌耐受、高应激诱导的渴望和酒精复发的风险。因此，这种压力系统功能障碍可能会危及早期戒酒期间的压力应对和酒精恢复。重要的临床前证据表明，去甲肾上腺素能中断可能有助于这些酒精相关的应激唤醒变化，α-1肾上腺素能拮抗剂，如哌唑嗪，可能使这些应激系统适应正常化，并减少酒精摄入。因此，我们假设，哌唑嗪将减少压力诱导的渴望和改善神经内分泌和自主神经反应的压力和酒精线索暴露在早期禁欲。其次，我们还评估了终生焦虑障碍对哌唑嗪作用的影响。40名住院寻求治疗的酒精依赖者被随机分配接受安慰剂（n=18）或16 mg/天，T.I.D.，哌唑嗪（n=22），以双盲方式，滴定超过2周。在达到全剂量后的第3-4周，患者以随机、平衡的顺序连续三天暴露于三种5分钟的个性化引导成像条件（压力提示、酒精提示、中性/放松提示）。酒精渴望，焦虑，心率，皮质醇和促肾上腺皮质激素水平进行了评估，在基线，以下图像和重复恢复时间点。哌唑嗪减少了压力线索诱导的酒精渴求（p<0.05）和压力和酒精线索诱导的焦虑（p<0.05）;并增加了所有想象条件下的心率反应（p<0.05）。与安慰剂相比，哌唑嗪降低了基础皮质醇和ACTH（p <0.05），并减弱了应激线索诱导的皮质醇升高（p<0.05）。最后，在那些没有终生焦虑症的人中，安慰剂组显示出压力和酒精线索诱导的皮质醇增加（p <0.05），而哌唑嗪组没有。哌唑嗪可减轻早期戒酒期间应激线索诱导的酒精渴求和焦虑，同时改善肾上腺素能和应激系统功能，这些作用与终生焦虑症病史无关。
Chronic alcohol results in changes to stress biology and autonomic arousal contributing to acute alcohol withdrawal symptoms, neuroendocrine tolerance of the hypothalamic-pituitary-adrenal (HPA) axis responses, high stress-induced craving, and risk of alcohol relapse. Thus, stress coping and recovery from alcohol during early abstinence may be jeopardized by such stress system dysfunction. Significant preclinical evidence suggests that noradrenergic disruption may contribute to these alcohol-related stress arousal changes and that alpha-1 adrenergic antagonists, such as prazosin, may normalize these stress system adaptations and reduce alcohol intake. Thus, we hypothesized that prazosin would reduce stress-induced craving and improve neuroendocrine and autonomic response to stress- and alcohol cue exposure during early abstinence. We secondarily also assessed the role of lifetime anxiety disorders on these prazosin effects. Forty inpatient treatment-seeking alcohol dependent individuals were randomly assigned to receive placebo (n=18) or 16mg/day, T.I.D., prazosin (n=22) in a double-blind manner, titrated over 2 weeks. In week 3–4 after achieving full dose, patients were exposed to three 5-minute personalized guided imagery conditions (stress cue, alcohol cue, neutral/relaxing cue), on three consecutive days in a random, counterbalanced order. Alcohol craving, anxiety, heart rate, cortisol and ACTH levels were assessed at baseline, following imagery and at repeated recovery timepoints. Prazosin reduced stress cue-induced alcohol craving (p<.05) and stress- and alcohol cue-induced anxiety (p<.05); and increased heart rate responses in all imagery conditions (p<.05). Prazosin lowered basal cortisol and ACTH (p’s<.05), and attenuated stress cue-induced rises in cortisol (p<.05) vs placebo. Finally, in those without lifetime anxiety disorder, the placebo group showed stress- and alcohol cue-induced increases in cortisol (p’s<.05), while the prazosin group did not. Prazosin may attenuate stress cue-induced alcohol craving and anxiety during early abstinence while improving adrenergic and stress system function, effects which are independent of a history of lifetime anxiety disorders.
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影响因子：
3.7
作者：
LANG, PJ;KOZAK, MJ;MCLEAN, A
通讯作者：
MCLEAN, A
影响因子：
2.3
作者：
Rasmussen, Dennis D.;Wilkinson, Charles W.;Raskind, Murray A.
通讯作者：
Raskind, Murray A.
影响因子：
3.7
作者：
Fox, HC;Talih, M;Sinha, R
通讯作者：
Sinha, R
影响因子：
3.2
作者：
Simpson, Tracy L.;Malte, Carol A.;Saxon, Andrew J.
通讯作者：
Saxon, Andrew J.
对成瘾风险和复发脆弱性的压力反应的中央和周围生物标志物。
影响因子：
13.6
作者：
Milivojevic V;Sinha R
通讯作者：
Sinha R