Department of Psychology, Brigham Young University, Provo, Utah.
Georgia State University, Atlanta, Georgia.
Alcohol Clin Exp Res. 2018 Feb;42(2):424-431. doi: 10.1111/acer.13552. Epub 2018 Jan 23.
Type 2 alcoholism is characterized by low serotonin system functioning and has a high degree of heritability, with offspring of alcoholics often showing a reduced response to the intoxicating effects of ethanol (EtOH), which is thought to be marker for future alcohol use disorders (AUDs). As such, an important aim of studies investigating the origins of AUDs is to understand the relationship between serotonin system functioning and level of intoxication. A nonhuman primate model was used to evaluate observational ratings of sensitivity to EtOH and to further investigate the relationship between central serotonin activity and behavioral response to EtOH.
Cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) were obtained from 4 cohorts of alcohol-naïve, adolescent rhesus macaques (N = 82, 45 females, 37 males). One to 3 months after the CSF sample, subjects were administered a standardized intravenous EtOH bolus (males: 2.1 g/kg body weight, females: 2.0 g/kg body weight), placed into an open-top, clear plexiglass chamber suspended from the ceiling, and their latency to escape was recorded as a measure of the degree of intoxication. Thereafter, subjects were rated using a Likert scale for the degree of intoxication during a 30-minute observation period.
Our results indicate that latency to escape from the chamber was associated with intoxication ratings (p = 0.0009) following the standardized intravenous administration of EtOH. Low CSF 5-HIAA concentrations predicted short escape latency (p = 0.007) and were associated with low intoxication ratings (p = 0.02), indicating that low central nervous system (CNS) serotonin functioning is related to relative insensitivity to the intoxicating effects of alcohol.
Our study shows that, in monkeys exposed to alcohol for the first time, objective measures of intoxication are associated with subjective ratings for intoxication, and both were associated with CSF 5-HIAA concentrations. Our data confirm and extend the finding that low CNS serotonin functioning is predictive of intrinsic low sensitivity to the intoxicating effects of EtOH.
2 型酒精中毒的特点是血清素系统功能低下，具有高度遗传性，酗酒者的后代往往对乙醇（EtOH）的致醉作用反应减弱，这被认为是未来酒精使用障碍（AUDs）的标志物。因此，研究 AUDs 起源的一个重要目标是了解血清素系统功能与醉酒程度之间的关系。本研究使用非人类灵长类动物模型来评估对 EtOH 的敏感性的观察性评分，并进一步研究中枢血清素活性与对 EtOH 的行为反应之间的关系。
从 4 个队列的酒精-naive 青少年恒河猴（N=82，45 只雌性，37 只雄性）中获得脑脊液（CSF）中的 5-羟吲哚乙酸（5-HIAA）浓度。CSF 样本采集后 1-3 个月，给动物单次静脉注射 EtOH （雄性：2.1g/kg 体重，雌性：2.0g/kg 体重），将其放入一个顶部敞开的透明有机玻璃室中，悬挂在天花板上，并记录其逃避潜伏期作为醉酒程度的衡量标准。之后，在 30 分钟的观察期间，通过李克特量表对动物的醉酒程度进行评分。
我们的结果表明，在标准化静脉注射 EtOH 后，从室中逃避的潜伏期与醉酒评分相关（p=0.0009）。CSF 中 5-HIAA 浓度低预示着逃避潜伏期短（p=0.007），并且与醉酒评分低相关（p=0.02），这表明中枢神经系统（CNS）中低血清素功能与对酒精致醉作用的相对不敏感有关。
我们的研究表明，在首次接触酒精的猴子中，客观的醉酒程度测量与主观的醉酒评分相关，两者都与 CSF 5-HIAA 浓度相关。我们的数据证实并扩展了低中枢血清素功能可预测对 EtOH 致醉作用的固有低敏感性的发现。
