Rimondini Roberto, Sommer Wolfgang, Heilig Markus
Division of Psychiatry, NEUROTEC Department, Karolinska Institute, M57 Huddinge University Hospital, S141 86 Stockholm, Sweden.
J Stud Alcohol. 2003 Jul;64(4):445-9. doi: 10.15288/jsa.2003.64.445.
Development of alcohol dependence is gradual, requires prolonged exposure to alcohol and reflects neuroadaptive processes in the brain. An understanding of these neuroadaptive processes can lead to novel treatment targets. We recently showed that 7 weeks of intermittent alcohol vapor exposure in rats induces a long-lasting increase of voluntary ethanol consumption, accompanied by changes in gene expression patterns in cingulate cortex and amygdala. These findings prompt the question of whether underlying adaptive processes develop gradually over time or whether a temporal threshold exists for this phenotype conversion to occur. We addressed this question by examining the functional consequences of different exposure durations.
Male Wistar rats (N = 43) were exposed to alcohol according to the previously published protocol for 2, 4 or 7 weeks. Following 3 weeks of abstinence to eliminate effects of acute withdrawal, subjects were introduced to voluntary alcohol self-administration in a two-bottle free-choice paradigm with continuous access.
Rats exposed to alcohol vapor for 7 weeks displayed a marked increase in voluntary ethanol consumption and a dramatic increase in ethanol preference. In rats exposed for shorter periods (2 and 4 weeks), neither ethanol self-administration nor ethanol preference were increased at any time point.
These observations support the existence of a temporal threshold for induction of long-lasting changes in voluntary alcohol consumption. The search for underlying molecular processes should be carried out in this context.
酒精依赖的发展是渐进的，需要长期接触酒精，且反映了大脑中的神经适应性过程。了解这些神经适应性过程有助于找到新的治疗靶点。我们最近发现，大鼠间歇性暴露于酒精蒸汽7周会导致自愿乙醇摄入量长期增加，并伴有扣带回皮质和杏仁核基因表达模式的变化。这些发现引发了一个问题，即潜在的适应性过程是随着时间逐渐发展的，还是存在一个时间阈值来促使这种表型转变的发生。我们通过研究不同暴露持续时间的功能后果来解决这个问题。
将43只雄性Wistar大鼠按照先前公布的方案暴露于酒精中2、4或7周。在禁欲3周以消除急性戒断效应后，让实验对象在两瓶自由选择模式下持续接触酒精，进行自愿酒精自我给药实验。
暴露于酒精蒸汽7周的大鼠自愿乙醇摄入量显著增加，对乙醇的偏好也急剧增加。在较短时间（2周和4周）暴露的大鼠中，在任何时间点乙醇自我给药量和对乙醇的偏好均未增加。
这些观察结果支持在诱导自愿酒精摄入量的长期变化方面存在时间阈值这一观点。应在此背景下寻找潜在的分子过程。
