Krystal J H, Webb E, Cooney N L, Kranzler H R, Southwick S W, Heninger G R, Charney D S
Department of Psychiatry, Yale University School of Medicine, New Haven, CT.
Am J Psychiatry. 1996 Jan;153(1):83-92. doi: 10.1176/ajp.153.1.83.
This study compared serotonergic (5-HT) and noradrenergic reactivity in recently detoxified alcoholic patients and healthy comparison subjects.
Participants were 22 male inpatients who met DSM-III-R criteria for alcohol dependence and who were abstinent for 12-26 days and 13 male healthy comparison subjects. Subjects completed 3 days of testing over 2 weeks under double-blind conditions that involved the intravenous infusions of m-chlorophenylpiperazine (mCPP), yohimbine, or a saline placebo. Drug effects on mood, physiologic responses, and plasma levels of cortisol, prolactin, and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured.
Both mCPP and yohimbine infusion increased nervousness, vital signs, and plasma cortisol, prolactin, and MHPG levels relative to placebo Cortisol responses to mCPP were blunted in the alcoholic patients relative to the comparison subjects. Cortisol and prolactin responses to yohimbine were greater in the alcoholic patients, whereas their pulse increases after yohimbine infusion were blunted. No group differences emerged in MHPG, nervousness, or blood pressure responses to either drug.
This study documents persistent alterations in neuroendocrine responsivity of both 5-HT and noradrenergic systems in alcoholic patients after detoxification. Blunted cortisol responses to mCPP in these recently detoxified patients may reflect reductions in 5-HT2 receptor function. The absence of altered MHPG responses to yohimbine in the alcoholic patients suggests that presynaptic noradrenergic responsivity is not persistently altered in these patients. In contrast, the enhanced cortisol responses and reduced pulse responses to yohimbine in alcoholic patients may reflect down-regulation of postsynaptic noradrenergic receptors.
本研究比较了近期戒酒的酒精依赖患者与健康对照者的5-羟色胺能（5-HT）和去甲肾上腺素能反应性。
参与者包括22名符合DSM-III-R酒精依赖标准且已戒酒12至26天的男性住院患者以及13名男性健康对照者。受试者在双盲条件下于2周内完成了为期3天的测试，测试内容包括静脉输注间氯苯哌嗪（mCPP）、育亨宾或生理盐水安慰剂。测量了药物对情绪、生理反应以及血浆皮质醇、催乳素和3-甲氧基-4-羟基苯乙二醇（MHPG）水平的影响。
与安慰剂相比，输注mCPP和育亨宾均增加了紧张感、生命体征以及血浆皮质醇、催乳素和MHPG水平。与对照者相比，酒精依赖患者对mCPP的皮质醇反应减弱。酒精依赖患者对育亨宾的皮质醇和催乳素反应更强，而输注育亨宾后他们的脉搏增加减弱。两组在对两种药物的MHPG、紧张感或血压反应方面均未出现差异。
本研究记录了酒精依赖患者戒酒后5-HT和去甲肾上腺素能系统神经内分泌反应性的持续改变。这些近期戒酒的患者对mCPP的皮质醇反应减弱可能反映了5-HT2受体功能的降低。酒精依赖患者对育亨宾的MHPG反应未改变，这表明这些患者突触前去甲肾上腺素能反应性并未持续改变。相比之下，酒精依赖患者对育亨宾的皮质醇反应增强和脉搏反应减弱可能反映了突触后去甲肾上腺素能受体的下调。
