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.

在先前接触乙醇且父母不在的情况下，恒河猴的口服酒精摄入量增加。 博士。陈和施万特进行了一系列研究，探讨早期接触酒精是否会导致晚年酒精摄入量增加。受试者在社会群体（MR）中与母亲一起长大，或者在纯同伴群体（PR）中独自长大。平均年龄为 3 岁时，动物被注射 2.2 克/公斤（雄性）或 2.0 克/公斤（雌性）静脉注射剂量的酒精，从而产生中毒。几个月后，受试者被允许饮用 8.4% 的阿斯巴甜酒精溶液。陈博士发现，经过静脉注射酒精预处理的动物摄入量更高。此外，PR 受试者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饮酒的风险增加，而成年早期不饮酒可能会加剧这种影响。施万特博士评估了青春期前幼猴的口服酒精摄入量，发现与青少年相比，较年轻的幼猴饮用更多的酒精。此外，青少年受试者在 6 周的测试中的饮酒模式有所不同：年龄较大的青少年在 6 周内的饮酒量几乎没有变化或增加，而幼年猴子在 6 周内的饮酒量却稳步下降。几周。稍后将对这些受试者进行测试，看看早期口服摄入是否会增加青少年的酗酒和摄入量。 中枢神经系统血清素周转率下降、生命早期的压力以及对乙醇的初始反应是青春期恒河猴乙醇消耗的预测因素。 博士。 Chen 和 Schwandt 还研究了中枢神经系统血清素活性、对酒精运动损伤作用的反应以及随后的饮酒之间的关系。获得脑脊液（CSF）后一个月，给动物注射与上述相同的静脉注射剂量的酒精，并评估中毒程度。随后允许动物在每天 1 小时的时间内自由饮用可口的酒精溶液，直到它们建立稳定的摄入量。早期父母缺席、低 CSF 5-HIAA 以及减少 2 gm/kg 剂量的酒精中毒是未来高酒精摄入量的预测因素。我们的研究结果表明，中枢神经系统血清素周转率低与对酒精的反应降低有关，并且是饮酒量增加的潜在风险因素。施万特博士评估了年龄对青春期猴子中毒水平的影响。她发现，当控制几个变量时，年轻的青少年比年长的青少年更容易喝醉。还存在一些性别差异，年轻女性表现出较少的跳跃障碍和酒精引起的运动刺激较少，而年轻男性则不太可能表现出酒精引起的攻击性。 恒河猴无限地获得社会乙醇口服自我给药：在压力后时期增加饮酒。研究人员对一群青少年雄性恒河猴进行了长期饮酒模式的研究，这些猕猴每天 24 小时饮用含阿斯巴甜的酒精溶液。结果显示，猴子在晚上（下午 4 点到凌晨 12 点）比白天工作时间（上午 8 点到下午 4 点）喝了更多的酒精。结果还表明，猴子在周末比工作日喝得更多。每日酒精摄入量最低的时间恰逢研究人员周一至周五的工作时间，以及捕捉邻近围栏中的猴子群进行科学研究的时间。这些发现表明，在潜在压力期间，恒河猴会抑制酒精摄入量，但与人类和啮齿类动物一样，当威胁不再存在时，猴子会在压力期后增加酒精摄入量。 教养、年龄、冲动控制和饮酒 很明显，在没有父母的情况下长大的受试者在免费饮酒时会消耗更多的酒精。然而，人们对产生如此高摄入量的机制知之甚少。我们与克劳迪娅·法尔克 (Claudia Fahlke) 合作，研究了父母（母亲）与有限的社会互动对发展的作用，并最终研究了父母（母亲）对青少年和成人酒精摄入量的不同影响。受试者作为对照组与父母一起饲养（MR），没有成人，但有不断的机会与同龄同伴互动（PR），或者作为代理同伴饲养（SPR）猴子，其社会经验有限。 SPR 猴子从出生起就被提供了一个覆盖着毛圈布的替代者，但与 PR 对象不同的是，它们的社交经历仅限于每天一到三个小时。 PR 受试者（有持续的社交互动，但没有成年人在场）和 SPR 受试者表现出高度焦虑，并且比 MR 受试者消耗更多的酒精。另一方面，当对各种挑战进行测试时，MR 和 PR 婴儿比 SPR 婴儿明显更少抑制和恐惧，并且当所有组都面临新环境的挑战时，PR 和 MR 婴儿都能够比 SPR 婴儿更好地调整和团体形成。此外，所有 SPR 受试者的社会支配地位（社会能力的敏感指标）均较低。尽管社交和情感行为存在这些差异，但 PR 和 SPR 受试者的饮酒率相同。 在 Schwandt 博士和她的工作人员进行的一系列实验中，我们假设 SPR 猴子会表现出冲动控制受损的证据，这是通过在入侵者挑战范式中与不熟悉的、具有潜在危险的入侵者的手臂长度所花费的时间来衡量的。在这个范例中，一只陌生的、同性别、同年龄的猴子被放置在与家庭笼子相邻的一个小笼子里。结果表明，与 MR 和 PR 成年猴相比，成年 SPR 动物在入侵者的手臂长度范围内花费的时间明显更多，这表明 SPR 受试者的冲动控制受损。这些发现表明，SPR 受试者中出现的类焦虑行为和社交缺陷不仅是父母缺席的结果，也是早期社交互动减少的结果。这些发现说明了对正常发育的不同影响，但考虑到 PR 和 SPR 受试者饮酒的比例相同，我们的研究结果表明，父母的影响在过量饮酒的风险中起着独立的作用。 多项证据表明，成年人饮酒量增加与冲动控制缺陷有关。然而，很少有研究关注青春期前受试者冲动控制缺陷与饮酒之间的关系。在另一项研究中，利用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量。使用上述相同的入侵者挑战测试，我们量化了受试者接近不熟悉的潜在危险入侵者的潜伏期。一年后，受试者被允许自由饮酒。有点令人惊讶的是，与之前对成年人的研究相比，青春期前的青少年表现出接近入侵者的延迟潜伏期，这表明这个年龄段的人可能对陌生人有高度的恐惧。与这种解释一致的是，在该年龄段内，接近陌生人的潜伏期增加与饮酒直接相关。我们的结果表明，高度焦虑和陌生人恐惧预示着青春期前猕猴的高饮酒量。