Section of Neurobiology, The University of Texas at Austin, Austin, TX 78712, USA.
Curr Biol. 2012 Dec 18;22(24):2338-41. doi: 10.1016/j.cub.2012.10.038. Epub 2012 Nov 29.
Physiological alcohol dependence is a key adaptation to chronic ethanol consumption that underlies withdrawal symptoms, is thought to directly contribute to alcohol addiction behaviors, and is associated with cognitive problems such as deficits in learning and memory. Based on the idea that an ethanol-adapted (dependent) animal will perform better in a learning assay than an animal experiencing ethanol withdrawal will, we have used a learning paradigm to detect physiological ethanol dependence in Drosophila. Moderate ethanol consumption initially degrades the capacity of larvae to learn, but they eventually adapt and are able to learn as well as ethanol-naive animals. However, withholding ethanol from ethanol-adapted larvae impairs learning. Ethanol reinstatement restores the capacity to learn, thus demonstrating cognitive dependence on ethanol. The larval nervous system also shows ethanol-withdrawal hyperexcitability. Larvae reach ethanol concentrations equivalent to 0.05 to 0.08 blood-alcohol concentration-levels that would be mildly intoxicating in humans. These ethanol-induced changes in learning are not the product of sensory deficits or state-dependent learning. This is the first demonstration of cognitive ethanol dependence in an invertebrate genetic model system.
生理性酒精依赖是慢性乙醇摄入的关键适应，它是戒断症状的基础，被认为直接导致了酒精成瘾行为，并与学习和记忆等认知问题有关。基于这样一种观点，即适应乙醇（依赖）的动物在学习测试中的表现将优于经历乙醇戒断的动物，我们已经使用学习范式在果蝇中检测生理性酒精依赖。适度的乙醇消耗最初会降低幼虫的学习能力，但它们最终会适应并能够像未接触乙醇的动物一样学习。然而，从适应乙醇的幼虫中去除乙醇会损害学习能力。乙醇的重新引入恢复了学习能力，从而证明了对乙醇的认知依赖。幼虫的神经系统也表现出乙醇戒断的过度兴奋。幼虫达到的乙醇浓度相当于 0.05 到 0.08 的血液酒精浓度水平，这在人类中会导致轻度醉酒。这些学习中的乙醇诱导变化不是感觉缺陷或状态依赖学习的结果。这是在无脊椎动物遗传模型系统中首次证明认知性乙醇依赖。
