Naranjo C A, Bremner K E
Psychopharmacology Research Program, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
EXS. 1994;71:209-19. doi: 10.1007/978-3-0348-7330-7_21.
The relationship between serotonin neurotransmission and alcohol consumption (AC) was first determined in preclinical studies. AC generally increases following treatments which decrease serotonin activity, and levels of 5-HT and metabolites are low in some brain regions of alcohol-preferring rats. Pharmacological treatments which enhance serotonergic neurotransmission (uptake inhibitors, releasers, agonists) consistently reduce AC in rats. Serotonin uptake inhibitors (SUI; e.g., citalopram, fluoxetine) have been studied extensively in humans. In several double-blind randomized, placebo-controlled trials, SUI consistently decreased short-term (2-4 weeks) AC by averages of 15% to 20% in nondepressed mildly/moderately dependent alcoholics who received no other treatment. Some subjects decreased AC by up to 60%. The effects of SUI on AC were dose-dependent and not related to side effects (few and mild) or changes in anxiety or depression (not observed). SUI decreased desire to drink and liking for alcohol, suggesting a mechanism of action, to be considered in the development of treatments to reduce AC and prevent relapse. However, while an adjunctive brief psychosocial intervention enhanced the short-term effect of a SUI, the long-term (12-week) effects of SUI and placebo were similar. Other drugs acting on the 5-HT system have been tested in humans, but results are inconclusive. For example, buspirone, a 5-HT1A receptor partial agonist, reduced anxiety and alcohol craving, but not AC; a 5-HT partial agonist, m-CPP, increased craving in abstinent alcoholics; modest reductions in AC were observed with a 5-HT3 antagonist, ondansetron (0.5 mg/day, but not 4 mg/day). Ritanserin, a 5-HT2 antagonist, reduced desire to drink and prevented relapse in a small (n = 5) study, and there was some indication that it reduced desire to drink and enhanced alcohol effects without reducing AC, in another study. The therapeutic potential of these medications is being studied. SUI and other serotonin-altering medications are promising new neuropharmacological treatments for AC.
血清素神经传递与酒精消费（AC）之间的关系最早是在临床前研究中确定的。在降低血清素活性的治疗后，AC通常会增加，在偏爱酒精的大鼠的某些脑区中，5-羟色胺（5-HT）及其代谢物的水平较低。增强血清素能神经传递的药物治疗（摄取抑制剂、释放剂、激动剂）持续降低大鼠的AC。血清素摄取抑制剂（SUI；如西酞普兰、氟西汀）已在人体中进行了广泛研究。在几项双盲随机、安慰剂对照试验中，SUI在未接受其他治疗的非抑郁轻度/中度依赖酒精者中持续降低短期（2 - 4周）AC，平均降低15%至20%。一些受试者的AC降低高达60%。SUI对AC的影响是剂量依赖性的，与副作用（少且轻微）或焦虑或抑郁的变化无关（未观察到）。SUI降低了饮酒欲望和对酒精的喜好，提示了一种作用机制，在开发降低AC和预防复发的治疗方法时应予以考虑。然而，虽然辅助性简短心理社会干预增强了SUI的短期效果，但SUI和安慰剂的长期（12周）效果相似。其他作用于5-羟色胺系统的药物已在人体中进行测试，但结果尚无定论。例如，5-HT1A受体部分激动剂丁螺环酮可减轻焦虑和酒精渴望，但不能降低AC；5-HT部分激动剂m-CPP增加了戒酒者的渴望；5-HT3拮抗剂昂丹司琼（0.5毫克/天，但不是4毫克/天）可适度降低AC。在一项小型（n = 5）研究中，5-HT2拮抗剂利坦色林降低了饮酒欲望并预防了复发，在另一项研究中，有迹象表明它降低了饮酒欲望并增强了酒精作用但未降低AC。这些药物的治疗潜力正在研究中。SUI和其他改变血清素的药物是有前景的新型神经药理学AC治疗方法。
