Roberto M, Nelson T E, Ur C L, Gruol D L
Department of Neuropharmacology and Alcohol Research Center, The Scripps Research Institute, La Jolla, California 92037, USA.
J Neurophysiol. 2002 May;87(5):2385-97. doi: 10.1152/jn.2002.87.5.2385.
Alcohol exposure induces multiple neuroadaptive changes in the CNS that can have serious long-term consequences on CNS function including cognitive effects and attenuation of learning and memory. The cellular mechanisms underlying the CNS effects of alcohol have yet to be fully elucidated and are likely to depend on the pattern and dose of alcohol exposure. Using electrophysiological recordings from hippocampal slices obtained from control and chronic alcohol-treated rats, we have investigated the effects of a binge pattern of alcohol abuse on synaptic plasticity in the CNS. The alcohol-treated animals were exposed to ethanol vapor for 12-14 days using an intermittent exposure paradigm (14 h ethanol exposure/10 h ethanol withdrawal daily; blood alcohol levels approximately 180 mg/dl), a paradigm that models human binge alcohol use. Induction of long-term potentiation (LTP) in the CA1 region of the hippocampus by tetanic stimulation of Schaffer collaterals was completely blocked in slices from the chronic alcohol-treated animals. LTP remained blocked 1 day after withdrawal of animals from alcohol, indicating that the neuroadaptive changes produced by alcohol were not readily reversible. Partial recovery was observed after withdrawal from alcohol for 5 days. Other measures of synaptic plasticity including posttetanic potentiation and paired-pulse facilitation were also altered by the intermittent alcohol treatment paradigm. The results suggest that alterations in synaptic plasticity induced by chronic intermittent ethanol consumption play an important role in the effects of binge alcohol use on learning and memory function.
酒精暴露会在中枢神经系统（CNS）中引发多种神经适应性变化，这些变化可能会对中枢神经系统功能产生严重的长期影响，包括认知效应以及学习和记忆能力的减弱。酒精对中枢神经系统产生影响的细胞机制尚未完全阐明，并且可能取决于酒精暴露的模式和剂量。我们利用从对照大鼠和慢性酒精处理大鼠获取的海马切片进行电生理记录，研究了酗酒的暴饮模式对中枢神经系统突触可塑性的影响。使用间歇性暴露范式（每天14小时乙醇暴露/10小时乙醇戒断；血液酒精水平约为180毫克/分升），将酒精处理的动物暴露于乙醇蒸气中12 - 14天，该范式模拟人类暴饮酒精的情况。在慢性酒精处理动物的切片中，通过强直刺激海马体CA1区的Schaffer侧支诱导的长时程增强（LTP）完全被阻断。在动物停止饮酒1天后，LTP仍然被阻断，这表明酒精产生的神经适应性变化不易逆转。在停止饮酒5天后观察到部分恢复。间歇性酒精处理范式也改变了其他突触可塑性指标，包括强直后增强和双脉冲易化。结果表明，慢性间歇性乙醇摄入诱导的突触可塑性改变在暴饮酒精对学习和记忆功能的影响中起重要作用。
