Eckardt M J, File S E, Gessa G L, Grant K A, Guerri C, Hoffman P L, Kalant H, Koob G F, Li T K, Tabakoff B
Office of Scientific Affairs, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA.
Alcohol Clin Exp Res. 1998 Aug;22(5):998-1040. doi: 10.1111/j.1530-0277.1998.tb03695.x.
The concept of moderate consumption of ethanol (beverage alcohol) has evolved over time from considering this level of intake to be nonintoxicating and noninjurious, to encompassing levels defined as "statistically" normal in particular populations, and the public health-driven concepts that define moderate drinking as the level corresponding to the lowest overall rate of morbidity or mortality in a population. The various approaches to defining moderate consumption of ethanol provide for a range of intakes that can result in blood ethanol concentrations ranging from 5 to 6 mg/dl, to levels of over 90 mg/dl (i.e., approximately 20 mM). This review summarizes available information regarding the effects of moderate consumption of ethanol on the adult and the developing nervous systems. The metabolism of ethanol in the human is reviewed to allow for proper appreciation of the important variables that interact to influence the level of exposure of the brain to ethanol once ethanol is orally consumed. At the neurochemical level, the moderate consumption of ethanol selectively affects the function of GABA, glutamatergic, serotonergic, dopaminergic, cholinergic, and opioid neuronal systems. Ethanol can affect these systems directly, and/or the interactions between and among these systems become important in the expression of ethanol's actions. The behavioral consequences of ethanol's actions on brain neurochemistry, and the neurochemical effects themselves, are very much dose- and time-related, and the collage of ethanol's actions can change significantly even on the rising and falling phases of the blood ethanol curve. The behavioral effects of moderate ethanol intake can encompass events that the human or other animal can perceive as reinforcing through either positive (e.g., pleasurable, activating) or negative (e.g., anxiolysis, stress reduction) reinforcement mechanisms. Genetic factors and gender play an important role in the metabolism and behavioral actions of ethanol, and doses of ethanol producing pleasurable feelings, activation, and reduction of anxiety in some humans/animals can have aversive, sedative, or no effect in others. Research on the cognitive effects of acute and chronic moderate intake of ethanol is reviewed, and although a number of studies have noted a measurable diminution in neuropsychologic parameters in habitual consumers of moderate amounts of ethanol, others have not found such changes. Recent studies have also noted some positive effects of moderate ethanol consumption on cognitive performance in the aging human. The moderate consumption of ethanol by pregnant women can have significant consequences on the developing nervous system of the fetus. Consumption of ethanol during pregnancy at levels considered to be in the moderate range can generate fetal alcohol effects (behavioral, cognitive anomalies) in the offspring. A number of factors--including gestational period, the periodicity of the mother's drinking, genetic factors, etc.--play important roles in determining the effect of ethanol on the developing central nervous system. A series of recommendations for future research endeavors, at all levels, is included with this review as part of the assessment of the effects of moderate ethanol consumption on the central nervous system.
适度饮用乙醇(饮用酒中的酒精)这一概念随着时间的推移不断演变,从认为这种摄入量不会使人醉酒且无伤害,到涵盖特定人群中被定义为“统计学上”正常的水平,以及公共卫生驱动的概念,即将适度饮酒定义为与人群中总体发病率或死亡率最低水平相对应的摄入量。定义适度饮用乙醇的各种方法所涵盖的摄入量范围,会导致血液乙醇浓度从5至6毫克/分升,到超过90毫克/分升(即约20毫摩尔)。本综述总结了关于适度饮用乙醇对成人和发育中的神经系统影响的现有信息。对人体中乙醇的代谢进行了综述,以便在口服乙醇后,能正确认识相互作用以影响大脑乙醇暴露水平的重要变量。在神经化学层面,适度饮用乙醇会选择性地影响γ-氨基丁酸(GABA)、谷氨酸能、血清素能、多巴胺能、胆碱能和阿片样物质神经元系统的功能。乙醇可直接影响这些系统,和/或这些系统之间的相互作用在乙醇作用的表现中变得很重要。乙醇对大脑神经化学作用的行为后果以及神经化学作用本身,在很大程度上与剂量和时间相关,甚至在血液乙醇曲线的上升和下降阶段,乙醇作用的全貌也可能发生显著变化。适度摄入乙醇的行为影响可能包括人类或其他动物通过积极(如愉悦、兴奋)或消极(如抗焦虑、减轻压力)强化机制可感知为具有强化作用的事件。遗传因素和性别在乙醇的代谢及行为作用中起重要作用,在某些人/动物中产生愉悦感、兴奋和减轻焦虑的乙醇剂量,在另一些人/动物中可能产生厌恶、镇静作用或无作用。对急性和慢性适度摄入乙醇的认知影响的研究进行了综述,尽管许多研究指出,适度饮酒的习惯消费者的神经心理参数有可测量的下降,但其他研究并未发现此类变化。最近的研究还指出,适度饮用乙醇对老年人的认知表现有一些积极影响。孕妇适度饮用乙醇会对胎儿发育中的神经系统产生重大影响。孕期以被认为处于适度范围内的水平饮用乙醇,可在后代中产生胎儿酒精效应(行为、认知异常)。包括妊娠期、母亲饮酒的周期性、遗传因素等在内的一些因素,在确定乙醇对发育中的中枢神经系统的影响方面起重要作用。作为对适度饮用乙醇对中枢神经系统影响评估的一部分,本综述还包括了针对各级未来研究工作的一系列建议。