慢性乙醇摄入和戒断通过 ERK 通路改变大鼠背侧纹状体的突触可塑性。
Alteration of synaptic plasticity in rat dorsal striatum induced by chronic ethanol intake and withdrawal via ERK pathway.
机构信息
Department of Physiology, Nanjing Medical University, Nanjing, China.
出版信息
Acta Pharmacol Sin. 2011 Feb;32(2):175-81. doi: 10.1038/aps.2010.199.
AIM
The dorsal striatum has been proposed to contribute to the formation of drug-seeking behaviors, leading to excessive and compulsive drug usage, such as addiction. The current study aimed to investigate the involvement of extracellular signal-regulated kinase (ERK) pathway in the modification of striatal synaptic plasticity.
METHODS
Ethanol was administered to rats in drinking water at concentration of 6% (v/v) for 30 days. Rats were sacrificed on day 10, 20, or 30 during ethanol intake or on withdrawal day 1, 3, or 7 following 30-d ethanol intake. The striata were removed either for electrophysiological recording or for protein immuno-blot analysis. Extracellular recording technique was used to record population spikes (PS) induced by high-frequency stimulation (HFS) in the dorsolateral striatum (DLS).
RESULTS
Corticostriatal long-term depression (LTD) was determined to be dependent upon ERK signaling. Chronic ethanol intake (CEI) attenuated ERK phosphorylation and LTD induction, whereas withdrawal for one day (W1D) potentiated ERK phosphorylation and LTD induction. These results showed that the impact of chronic ethanol intake and withdrawal on corticostriatal synaptic plasticity was associated with ethanol's effect on ERK phosphorylation. In particular, pharmacological inhibition of ERK hyper-phosphorylation by U0126 prevented LTD induction in the DLS and attenuated ethanol withdrawal syndrome as well.
CONCLUSION
In rat DLS, chronic ethanol intake and withdrawal altered LTD induction via ERK signaling pathway. Ethanol withdrawal syndrome is mediated, at least partly, by ERK hyper-phosphorylation in the DLS.
目的
背侧纹状体被认为有助于形成觅药行为，导致过度和强迫性药物使用，如成瘾。本研究旨在探讨细胞外信号调节激酶（ERK）通路在纹状体突触可塑性改变中的作用。
方法
将乙醇以 6%（v/v）的浓度添加到大鼠饮用水中，连续 30 天。在摄入乙醇的第 10、20 或 30 天或在摄入 30 天乙醇后的第 1、3 或 7 天，处死大鼠。取出纹状体，用于电生理记录或蛋白质免疫印迹分析。使用细胞外记录技术记录高频刺激（HFS）在背外侧纹状体（DLS）中诱导的群体峰（PS）。
结果
皮质纹状体长时程抑制（ LTD ）依赖于 ERK 信号转导。慢性乙醇摄入（CEI）减弱了 ERK 磷酸化和 LTD 的诱导，而一天的戒断（W1D）增强了 ERK 磷酸化和 LTD 的诱导。这些结果表明，慢性乙醇摄入和戒断对皮质纹状体突触可塑性的影响与乙醇对 ERK 磷酸化的影响有关。特别是，U0126 抑制 ERK 过度磷酸化可防止 DLS 中 LTD 的诱导，并减轻乙醇戒断综合征。
结论
在大鼠 DLS 中，慢性乙醇摄入和戒断通过 ERK 信号通路改变 LTD 的诱导。乙醇戒断综合征至少部分是通过 DLS 中 ERK 的过度磷酸化介导的。
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