Goodwin F K
Alcohol, Drug Abuse, and Mental Health Administration, Rockville, MD 20857.
Public Health Rep. 1988 Nov-Dec;103(6):569-74.
Prospects for research advances in alcoholism are very promising, because of the explosion in the neurosciences and advances in epidemiology and typology of the disorder. For example, the field is now ready for molecular genetics studies of the early onset form of alcoholism that is transmitted from father to son with high penetrance. Leading neuroscientists are being recruited into alcoholism research. Paradoxically, this time of new hope coincides with challenges to the scientific enterprise, such as the animal rights movement and impatience with the scientific process in the face of the public health emergencies represented by acquired immunodeficiency syndrome (AIDS) and drug abuse. The emergence of genetically based subtypes of alcoholism suggests that at least two discrete illness processes are involved. Mounting evidence from spinal fluid studies has rekindled interest in a key role for serotonin in the early onset form of alcoholism. One hypothesis now being explored is that genetically low brain serotonin function may be part of the predisposition to this form of alcoholism. It is known that acute alcohol intake transiently increases brain serotonin turnover. Thus, drinking might be viewed as an attempt to correct a deficit, only to produce further serotonin depletion as the drug's effect wears off, setting up a vicious cycle of repeated attempts to self-medicate. Impulsive, violent, and suicidal behavior as well as alcohol abuse are associated with the low brain serotonin activity. Persons with these problems suffer from circadian rhythm and glucose metabolism disturbances that may also be mediated by serotonin. New pharmacological probes are now available to tease out the mechanisms of altered serotonin function. The progressively deteriorating course of severe episodic alcoholism in many ways parallels the process of electrically kindled seizures in experimental animals. There is evidence that repeated withdrawal episodes may kindle a worsening course, including phobic disorders, perhaps by triggering a hyper-reactive noradrenalin system.
由于神经科学的迅猛发展以及该疾病流行病学和类型学的进步，酒精中毒研究取得进展的前景十分广阔。例如，该领域现已准备好对早发性酒精中毒进行分子遗传学研究，这种类型的酒精中毒具有高外显率，可由父亲传给儿子。顶尖的神经科学家正被招募到酒精中毒研究领域。矛盾的是，这个充满新希望的时期恰逢科学事业面临挑战，比如动物权利运动，以及面对由获得性免疫缺陷综合征（艾滋病）和药物滥用所代表的公共卫生紧急情况时，公众对科学进程缺乏耐心。基于基因的酒精中毒亚型的出现表明，至少涉及两个不同的发病过程。脑脊液研究中越来越多的证据重新燃起了人们对血清素在早发性酒精中毒中关键作用的兴趣。目前正在探索的一种假设是，大脑血清素功能在基因层面较低可能是这种酒精中毒易感性的一部分。众所周知，急性饮酒会短暂增加大脑血清素的更新率。因此，饮酒可能被视为一种纠正缺陷的尝试，但随着药物效果消退，只会导致血清素进一步耗竭，从而形成自我治疗的恶性循环。冲动、暴力和自杀行为以及酒精滥用都与大脑血清素活性低有关。有这些问题的人会出现昼夜节律和葡萄糖代谢紊乱，这也可能由血清素介导。现在有了新的药理学探针来梳理血清素功能改变的机制。严重发作性酒精中毒的病情逐渐恶化，在许多方面与实验动物中电点燃癫痫的过程相似。有证据表明，反复的戒断发作可能会引发病情恶化，包括恐惧症，这可能是通过触发一个反应过度的去甲肾上腺素系统实现的。
