Higley J D, Suomi S J, Linnoila M
Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health Animal Center, Poolesville, Maryland 20837, USA.
Alcohol Clin Exp Res. 1996 Jun;20(4):629-42. doi: 10.1111/j.1530-0277.1996.tb01665.x.
Developmental, biochemical, and behavioral concomitants of excessive alcohol consumption were investigated using a nonhuman primate model. The variables of interest were: (1) interindividual stability of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) from infancy to adulthood, (2) effect of parental deprivation early in life on adult CSF 5-HIAA concentrations; (3) correlations between CSF 5-HIAA and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations and alcohol consumption; and (4) correlation between the frequency of competent social behaviors and alcohol consumption. Twenty-nine rhesus macaques were reared for their first 6 months either with their mothers or without adults in peer-only conditions. At 6 and 50 months of age, each subject underwent a series of four, 4-day social separations. Cisternal CSF was sampled before and during the first and last separations; concomitantly, observational data were collected on social dominance behavior in the home-cage. When they reached 50 months of age, the monkeys were provided free access to a palatable alcohol solution daily for 1-hr periods before, during, and after the social separations. Before and after the 50-month separations, data were collected on all types of social behavior in the home-cage. Results showed that peer-reared subjects consumed more alcohol than mother-reared subjects during baseline conditions. Mother-reared subjects, however, increased their rates of consumption to equal peer-reared subjects' rates of consumption during the conditions of a social separation stressor. Peer-reared subjects also exhibited lower CSF 5-HIAA concentrations in infancy and adulthood than their mother-reared counterparts. With rearing condition held constant, interindividual differences in CSF 5-HIAA, MHPG, and homovanillic acid were stable from infancy to adulthood, and high rates of alcohol were consumed by the young adult monkeys with low CSF 5-HIAA and MHPG concentrations, particularly when the CSF was obtained during the social separations. High rates of alcohol consumption were also observed in subjects with infrequent social interactions and less competent social behaviors. In contrast to the human data, we found no gender differences in rates of alcohol consumption, nor in the correlations between alcohol consumption and the other variables. With some exceptions, findings from the study are generally consistent with predictions from Cloninger's type II model of excessive alcohol consumption in men with low CSF 5-HIAA, who also exhibit impaired impulse control and violent and antisocial behaviors.
利用非人灵长类动物模型研究了过度饮酒的发育、生化和行为伴随情况。感兴趣的变量包括：（1）从婴儿期到成年期脑脊液（CSF）中5-羟吲哚乙酸（5-HIAA）的个体间稳定性；（2）生命早期父母剥夺对成年期脑脊液5-HIAA浓度的影响；（3）脑脊液5-HIAA与3-甲氧基-4-羟基苯乙二醇（MHPG）浓度及酒精摄入量之间的相关性；以及（4）胜任社交行为频率与酒精摄入量之间的相关性。29只恒河猴在出生后的前6个月要么与母亲一起饲养，要么在只有同伴的环境中由无成年动物陪伴饲养。在6个月和50个月大时，每只猴子都经历了一系列为期4天的4次社会隔离。在第一次和最后一次隔离之前和期间采集脑池脑脊液样本；同时，收集笼内社交优势行为的观察数据。当猴子达到50个月大时，在社会隔离之前、期间和之后，每天为它们提供1小时的美味酒精溶液自由饮用。在50个月的隔离前后，收集笼内所有类型社交行为的数据。结果显示，在基线条件下，由同伴饲养的猴子比由母亲饲养的猴子饮酒量更多。然而，在社会隔离应激条件下，由母亲饲养的猴子的饮酒量增加到与由同伴饲养的猴子相同的水平。由同伴饲养的猴子在婴儿期和成年期的脑脊液5-HIAA浓度也低于由母亲饲养的猴子。在饲养条件保持不变的情况下，从婴儿期到成年期，脑脊液5-HIAA、MHPG和高香草酸的个体间差异是稳定的，脑脊液5-HIAA和MHPG浓度低的年轻成年猴子饮酒量高，特别是在社会隔离期间采集脑脊液时。在社交互动不频繁且社交行为能力较差的猴子中也观察到高饮酒率。与人类数据不同的是，我们发现饮酒率以及饮酒与其他变量之间的相关性没有性别差异。除了一些例外情况，该研究的结果总体上与克隆宁格关于脑脊液5-HIAA低的男性过度饮酒的II型模型的预测一致，这些男性还表现出冲动控制受损以及暴力和反社会行为。
