Stevenson Rebekah A, Besheer Joyce, Hodge Clyde W
Bowles Center for Alcohol Studies, Department of Psychiatry, Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Psychopharmacology (Berl). 2008 Apr;197(3):361-70. doi: 10.1007/s00213-007-1038-y. Epub 2007 Dec 22.
The mammalian adolescent period is characterized by enhanced vulnerability to drug-induced neuroadaptations. Epidemiological evidence indicates that individuals who start drinking alcohol during adolescence are four times more likely to develop alcohol dependence in adulthood, but little is known about the adaptive mechanism(s) that may underlie this observation. Behavioral sensitization in rodents is a model of neurobehavioral plasticity that occurs following repeated drug exposure and may underlie components of addiction.
The goal of this study was to determine if adolescent mice are differentially sensitive to ethanol-induced locomotor sensitization as compared to adults.
Adolescent and adult DBA/2J mice were treated with saline or ethanol (1.0, 1.5, 2.0, 2.5 g/kg) for 7, 11, or 15 days and tested for acute and sensitized locomotor activity. Blood ethanol clearance (BEC) was also assessed 10, 60, and 180 min following treatment with ethanol 2 g/kg.
Adolescent mice were more sensitive than adult mice to the acute locomotor activating effects of ethanol. However, adolescent mice were less sensitive than adult mice to locomotor sensitization, as only the highest dose of ethanol (2.5 g/kg) induced sensitization in the adolescent mice, while lower doses of ethanol elicited sensitization in the adult mice. The differential response to ethanol sensitization was not related to duration of treatment or differential BEC.
These results indicate that adolescent mice are less sensitive to ethanol sensitization, and this blunted behavioral response in adolescents might reflect differential ethanol-induced neurobehavioral adaptations.
哺乳动物的青春期具有对药物诱导的神经适应性增强的易感性特征。流行病学证据表明，在青春期开始饮酒的个体在成年后发展为酒精依赖的可能性是其他人的四倍，但对于这一现象背后可能的适应性机制知之甚少。啮齿动物的行为敏化是一种神经行为可塑性模型，它发生在反复接触药物之后，可能是成瘾的组成部分。
本研究的目的是确定与成年小鼠相比，青春期小鼠对乙醇诱导的运动敏化是否具有不同的敏感性。
将青春期和成年DBA/2J小鼠用生理盐水或乙醇（1.0、1.5、2.0、2.5 g/kg）处理7、11或15天，并测试急性和敏化运动活性。在用2 g/kg乙醇处理后10、60和180分钟也评估了血液乙醇清除率（BEC）。
青春期小鼠比成年小鼠对乙醇的急性运动激活作用更敏感。然而，青春期小鼠对运动敏化的敏感性低于成年小鼠，因为只有最高剂量的乙醇（2.5 g/kg）在青春期小鼠中诱导了敏化，而较低剂量的乙醇在成年小鼠中引起了敏化。对乙醇敏化的差异反应与治疗持续时间或BEC差异无关。
这些结果表明，青春期小鼠对乙醇敏化的敏感性较低，而青少年这种减弱的行为反应可能反映了乙醇诱导的不同神经行为适应性。
