Alcohol Consumption, Impaired Impulses and Temperament

饮酒、冲动和气质受损

• 批准号: 7146655
• 负责人: James Dee Higley
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7146655
• 关键词: Macaca mulatta; age difference; alcoholic beverage consumption; alcoholism /alcohol abuse; alcoholism /alcohol abuse chemotherapy; animal developmental psychology; anxiety; behavior prediction; behavioral /social science research tag; behavioral genetics; buspirone; early experience; fluoxetine; genetic mapping; genetic polymorphism; genetic susceptibility; impulsive behavior; ketamine; mental disorder chemotherapy; neurotransmitter metabolism; nutrition related tag; parent deprivation; personality; positron emission tomography; self destructive behavior; serotonin; serotonin inhibitor; serotonin transporter

Increased oral alcohol intake in rhesus macaques after prior exposure to ethanol and parental absence. Drs. Chen and Schwandt performed a series of studies examining whether early exposure to alcohol would lead to an increased intake of alcohol later in life. Subjects were reared with their mothers in social groups (MR) or without adults in peer-only groups (PR). At a mean age of 3 years, animals were administered a 2.2 gm/kg (males) or 2.0 gm/kg (females) IV dose of alcohol that produced intoxication. Months later, subjects were allowed to drink an 8.4% aspartame-sweetened alcohol solution. Dr. Chen found higher intake in the animals that were pretreated with IV alcohol. Furthermore, alcohol intake was particularly higher in the PR than in the MR subjects. These results revealed that exposure to alcohol early in life may lead to an increased risk for high consumption and that early adult absence may exacerbate this effect. Dr. Schwandt assessed oral alcohol intake in preadolescent juveniles and found that when compared to adolescents, younger juvenile monkeys drink more alcohol. Furthermore, the pattern of consumption over the 6 weeks of testing is different in juvenile subjects: whereas older adolescents show little change or an increase in alcohol consumption across the 6 weeks, juvenile monkeys show a steady decrease in the amount of alcohol consumed across the 6 weeks. These subjects will be tested later to see if early oral intake augments adolescent alcohol binging and intake. Decreased CNS serotonin turnover, early-life stress, and initial response to ethanol are predictors of ethanol consumption in adolescent rhesus macaques. Drs. Chen and Schwandt also examined the relationship between CNS serotonin activity, the response to the motor-impairing effects of alcohol, and subsequent alcohol consumption,. One month after cerebrospinal fluid (CSF) was obtained, animals were administered the same IV doses of alcohol described above and rated for degree of intoxication. Animals were later allowed to freely consume a palatable alcohol solution in daily 1-hr sessions until they established a stable intake. Early parental absence, low CSF 5-HIAA, and decreased intoxication to the 2 gm/kg dose of alcohol were predictive of future high alcohol intake. Our findings suggest that low CNS serotonin turnover rate is related to a decreased response to alcohol and is a potential risk factor for increased alcohol consumption. Dr. Schwandt assessed the effects of age on levels of intoxication in adolescent monkeys. She found that when several variables were controlled, younger adolescents were more intoxicated than the older adolescents. There were also several sex differences with younger females showing fewer impaired leaps and less alcohol-induced motor stimulation, while younger males were less likely to show alcohol-induced aggression. Unlimited access to social ethanol oral self-administration in rhesus macaques: increased drinking during post-stress periods. Chronic alcohol consumption patterns were examined in a social group of adolescent male rhesus macaques given daily 24-hour access to the aspartame-sweetened alcohol solution. Results showed that the monkeys drank more alcohol in the evening, from 4PM to 12AM, than during day-light working hours from 8AM to 4PM. The results also showed that the monkeys drank more during the weekend than the weekdays. The lowest daily intake in alcohol consumption coincided with the Monday-Friday working hours of the research staff, and the hours in which groups of monkeys in adjacent enclosures were captured for scientific study. These findings suggest that during periods of potential stress, rhesus monkeys suppress alcohol intake but as in humans and rodents, monkeys increase their alcohol intake following stressful periods when a threat is no longer present. Rearing, Age, Impulse Control and Alcohol Consumption It is clear that subjects reared without parents consume more alcohol when it is freely available. However, little is known about the mechanisms that produce such high intake. In collaboration with Claudia Fahlke, we investigated the roles of parents (mothers) vs limited social interactions on development, and ultimately as differential contributors to adolescent and adult alcohol intake. Subjects were reared as controls with their parents (MR), without adults but with constant opportunities to interact with same aged peers (PR), or with limited social experience as surrogate-peer-reared (SPR) monkeys. SPR monkeys are provided with a terrycloth-covered surrogate from birth but unlike PR subjects, are limited in their social experiences to a period of one to three hours per day. The PR subjects (which have constant social interactions but no adults present) and SPR subjects exhibit high anxiety and consume more alcohol than MR subjects. On the other hand, when tested over a variety of challenges, MR and PR infants were significantly less inhibited and fearful than SPR infants, and both PR and MR infants were able to adjust better than SPR infants when all groups were challenged with a novel environment and group formation. Furthermore, all of the SPR subjects were low in social dominance rank, a sensitive measure of social competence. Despite these differences in social and emotional behavior, PR and SPR subjects were found to consume alcohol at equal rates. In a series of performed by Dr. Schwandt and her staff, we hypothesized that SPR monkeys would show evidence of impaired impulse control, as measured by time spent in arms length of an unfamiliar, potentially dangerous intruder, during an Intruder Challenge paradigm. In this paradigm an unfamiliar, same-sexed and same-aged monkey was placed in a small cage adjacent to the home cage. The results showed that the adult SPR animals spent significantly more time within arms length of the intruder when compared to both MR and PR adult monkeys, suggesting impaired impulse control in SPR subjects. These findings suggest that the anxiety-like behaviors and social deficits seen in the SPR subjects are not just a result of parental absence but are also a consequence of early decreased social interactions. Such findings illustrate different influences on normal development but given that the PR and SPR subjects consume alcohol at an equal rate, our findings suggest that parent influence plays an independent role in the risk for excessive alcohol intake. Several lines of evidence suggest an association of increased alcohol consumption with impulse control deficits in adults. Yet, few studies have focused on the relationship between impulse control deficits and alcohol consumption in preadolescent subjects. In another study, individual differences in the time to approach a stranger at one year of age were used to predict voluntary alcohol consumption at two years of age. Using the same Intruder Challenge Test described above, we quantified the subject?s latency to approach an unfamiliar potentially dangerous intruder. One year later subjects were allowed to freely consume alcohol. Somewhat surprisingly, when compared to previous studies on adults, the preadolescents displayed a delayed latency to approach the intruder, suggesting perhaps high stranger fear in this age group. Consistent with such an interpretation, within that age group an increased latency to approach the stranger directly correlated with alcohol consumption. Our results showed that high anxiety and stranger fear predict high alcohol consumption in preadolescent macaques.

先前暴露于乙醇和父母缺席后，恒河猴的口服酒精摄入量增加。 博士。 Chen和Schwandt进行了一系列研究，研究了早期饮酒是否会导致生命以后的酒精摄入量增加。在社会群体（MR）或不同行群体（PR）中，受试者与母亲在社会群体（MR）或没有成年人中抚养长大。在平均3岁时，将动物施用2.2 gm/kg（雄性）或2.0 gm/kg（女性）IV剂量的酒精剂量。几个月后，受试者被允许喝8.4％的阿斯巴甜饮酒溶液。 Chen博士发现，用静脉酒精预处理的动物摄入量更高。此外，PR的酒精摄入量特别高于MR受试者。这些结果表明，生命早期接触酒精可能会导致高消费的风险增加，而成年人的早期缺勤可能会加剧这种影响。施万德（Schwandt）博士评估了幼年青少年的口服酒精摄入量，发现与青少年相比，年轻的少年猴子喝更多的酒精。此外，在少年受试者中，在6周的测试中消费模式不同：而在6周内，年长的青少年几乎没有变化或饮酒量的增加，但少年猴子在6周内消耗的酒精含量稳步下降。这些受试者将在稍后进行测试，以查看早期口服摄入量是否增加了青春期酒精饮料和摄入量。 中枢神经系统5-羟色胺更新，早期应激和对乙醇的初始反应减少是青少年恒河猕猴中乙醇消耗的预测指标。 博士。 Chen和Schwandt还研究了CNS 5-羟色胺活性，对酒精运动效应的反应以及随后的酒精消耗之间的关系。在获得脑脊液（CSF）后一个月，对动物进行了与上述相同的静脉注射剂量的饮酒，并将其定为中毒程度。后来，允许动物在每天的1小时课程中自由食用可口的酒精溶液，直到它们建立稳定的摄入量为止。早期的父母缺席，低CSF 5-HIAA以及对2gm/kg酒精剂量的中毒降低可预测未来的高酒精摄入量。我们的发现表明，低中枢神经系统5-羟色胺转换率与对酒精的反应降低有关，并且是饮酒量增加的潜在危险因素。 Schwandt博士评估了年龄对青少年猴子中毒水平的影响。她发现，当控制了几个变量时，年轻的青少年比老年青少年更陶醉。年轻的女性也存在几种性别差异，表现出较少的飞跃受损，而酒精引起的运动刺激较少，而年轻的男性则表现出酒精引起的侵略性。 在恒河猕猴中无限制地获得社会乙醇口服自我给药：在压力后饮酒增加。在每天24小时进入阿斯巴甜饮酒解决方案的社交群体中，检查了一个青春期雄鹿猕猴的慢性饮酒模式。结果表明，猴子在晚上从下午4点到凌晨12点喝的酒精多于从上午8点至下午4点在日间工作时间里喝的酒精。结果还表明，猴子在周末喝的比工作日更多。饮酒的每日最低摄入量与研究人员的星期一至周五工作时间相吻合，以及捕获相邻围栏中的猴子群以进行科学研究的时间。这些发现表明，在潜在的压力时期，恒河猴抑制酒精摄入量，但是在人类和啮齿动物中，猴子在不再存在威胁的压力时期内增加了酒精摄入量。 饲养，年龄，冲动控制和饮酒 很明显，在没有父母的情况下饲养的受试者在自由使用时会消耗更多的酒精。但是，对产生如此高摄入量的机制知之甚少。与克劳迪娅·法赫克（Claudia Fahlke）合作，我们调查了父母（母亲）与有限的社会互动在发展中的作用，最终是对青少年和成人酒精摄入的差异贡献者。受试者与父母（MR）的对照组饲养，没有成年人，但有机会与同一老年同龄人（PR）互动，或者与代孕（SPR）猴子（SPR）猴子的社交经验有限。从出生开始，Spr猴子的社会经历从出生开始，但与公关学科不同，每天一到三个小时都有限制。 PR受试者（具有持续的社交互动，但没有成年人）和SPR受试者表现出高度的焦虑，并且与MR受试者相比，饮酒更多。另一方面，当在各种挑战中进行测试时，MR和PR婴儿的抑制和恐惧与SPR婴儿的抑制和恐惧明显少得多，而PR和MR婴儿在所有群体都受到新颖的环境和团体形成的挑战时，PR和MR都能比SPR婴儿进行更好的调整。此外，所有SPR主题的社会优势等级都低，这是对社会能力的敏感度量。尽管在社会和情感行为上存在这些差异，但发现PR和SPR受试者以同样的速度食用酒精。 在Schwandt博士及其员工的一系列表演中，我们假设Spr猴子会显示出冲动控制受损的证据，这是通过在入侵者挑战范式中花费的时间长度在陌生的，潜在危险的入侵者的武器长度上衡量的。在这个范式中，将一个陌生的，同性和相同的猴子放在家居笼子附近的一个小笼子里。结果表明，与MR和PR成人猴子相比，成年SPR动物在入侵者的手臂长度内花费了更多的时间，这表明SPR受试者的冲动控制受损。这些发现表明，在SPR受试者中看到的类似焦虑的行为和社会缺陷不仅是父母缺席的结果，而且也是早期减少社会互动的结果。这样的发现说明了对正常发育的不同影响，但是鉴于PR和SPR受试者以同样的速度食用酒精，我们的发现表明，父母影响在过度酒精摄入的风险中起着独立的作用。 几条证据表明，饮酒量增加与成年人冲动控制缺陷的关联。然而，很少有研究重点是脉冲控制缺陷与饮酒量之间的关系。在另一项研究中，使用在一岁时接近陌生人的时间的个体差异来预测两岁时的自愿饮酒。使用上述相同的入侵者挑战测试，我们量化了受试者的潜伏期，以接近陌生的潜在危险入侵者。一年后，受试者被允许自由饮酒。令人惊讶的是，与先前对成年人的研究相比，前少将表现出延迟的潜伏期来接近入侵者，这表明该年龄段的陌生人恐惧可能很高。与这种解释一致，在该年龄组中，延迟的潜伏期增加了与饮酒直接相关的陌生人。我们的结果表明，高焦虑和陌生人的恐惧预示着前猕猴的饮酒量高。