Petrakis Ismene L, Kerfoot Karin, Pittman Brian, Perrino Albert, Koretski Julia, Newcomb Jenelle, Limoncelli Diana, Acampora Gregory, Ralevski Elizabeth
NIAAA Center for the Translational Neuroscience of Alcoholism and Department of Psychiatry, Yale University School of Medicine, Connecticut, USA ; Department of Veterans Affairs, Alcohol Research Center, VA Connecticut Healthcare System, Connecticut, USA.
J Addict Res Ther. 2012 May 14;Suppl 7(2). doi: 10.4172/2155-6105.S7-002.
The development of alcohol use disorders is genetically influenced, and may be mediated through differences in the subjective response to alcohol. There is some evidence to suggest that response differences to alcohol could be conveyed by heritable differences in GABA receptors. The purpose of this study was to investigate whether individuals with a family history positive (FHP) for alcohol dependence would experience alterations in response to the GABA receptor agonist thiopental, in comparison to family history negative (FHN) subjects.
73 subjects (24 FHP and 49 FHN) between the ages of 21 and 30 years were administered sub-anesthetic doses of the GABA receptor agonist thiopental and placebo on two separate test days. Various alcohol-related measures were administered, including those examining subjective effects, coordination, and cognition.
Sub-anesthetic doses of thiopental produced alcohol-like subjective effects, as well as alcohol-like impaired coordination and cognition in healthy subjects. While there were no significant main effects in subjective, coordination, or cognitive effects between FHP and FHN individuals, analysis of peak effects suggested FHP had blunted sedative, but not stimulant effects compared to FHN.
Thiopental produced alcohol-like effects and perceived similarities to alcohol in healthy individuals. Subtle differences in sedative effects are consistent with reports of blunted FHP response to the negative but not stimulant effects of alcohol. Future studies are needed to better understand how this insight informs our understanding of the heritable risk for alcoholism and the treatment of alcohol use disorders.
酒精使用障碍的发生受遗传影响,可能通过对酒精主观反应的差异介导。有证据表明,对酒精反应的差异可能由γ-氨基丁酸(GABA)受体的遗传差异传递。本研究的目的是调查与家族史阴性(FHN)受试者相比,酒精依赖家族史阳性(FHP)个体对GABA受体激动剂硫喷妥钠的反应是否会发生改变。
在两个不同的测试日,对73名年龄在21至30岁之间的受试者(24名FHP和49名FHN)给予亚麻醉剂量的GABA受体激动剂硫喷妥钠和安慰剂。进行了各种与酒精相关的测量,包括那些检查主观效应、协调能力和认知能力的测量。
亚麻醉剂量的硫喷妥钠在健康受试者中产生了类似酒精的主观效应,以及类似酒精的协调能力和认知能力受损。虽然FHP和FHN个体在主观、协调或认知效应方面没有显著的主效应,但峰值效应分析表明,与FHN相比,FHP的镇静作用减弱,但兴奋作用未减弱。
硫喷妥钠在健康个体中产生了类似酒精的效应,并与酒精有相似的感知。镇静作用的细微差异与FHP对酒精负面但非兴奋作用反应减弱的报道一致。未来需要进一步研究,以更好地理解这一见解如何增进我们对酒精中毒遗传风险和酒精使用障碍治疗的理解。