Xie Gui Qin, Wang Shen Jun, Li Jing, Cui Sheng Zhong, Zhou Rong, Chen Ling, Yuan Xiao Ru
Department of Physiology, Nanjing Medical University, Nanjing, China.
Alcohol Clin Exp Res. 2009 Jan;33(1):121-8. doi: 10.1111/j.1530-0277.2008.00818.x. Epub 2008 Oct 18.
The striatum has been implicated to play a role in the control of voluntary behavior, and striatal synaptic plasticity is involved in instrumental learning. Ethanol is known to alter synaptic plasticity, in turn altering the behavior of human and animals. However, it remains unclear whether the striatum plays a role in the effects of ethanol on the central nervous system. The objective of this investigation was to study the effects of acute perfusion of ethanol on long-term potentiation (LTP) to elucidate the mechanisms of addictive drugs in the striatum. In addition, we investigated the contribution of intracellular extracellular signal regulated protein kinase (ERK) signaling pathway to corticostriatal LTP induction.
The stimulation evoked population spikes (PS) were recorded from the dorsomedial striatum (DMS) slices of rat using the extracellular recording technique. The LTP in DMS slices was induced by high-frequency stimulation (HFS). The ERK level of the DMS was assessed with the Western blot technique.
U0126, the inhibitor of ERK, eliminated or significantly attenuated the LTP induced by HFS of the PS in the DMS. MK801 and APV, N-methyl-d-aspartic acid receptor (NMDAR) antagonists, inhibited the induction of striatal LTP, and HFS-induced ERK activation decreased in the slices treated with MK801 in the DMS. Clinically relevant concentrations of ethanol (22 to 88 mM) dose-dependently attenuated the HFS-induced striatal LTP and ERK activation in this brain region.
The LTP of the PS in the DMS is, at least partly, mediated by the ERK pathway coupling to NMDARs. Ethanol attenuated the HFS-induced, ERK-mediated LTP in a dose-dependent manner in this brain region. These results indicate that ethanol may change the synaptic plasticity of corticostriatal circuits underlying the learning of goal-directed instrumental actions, which is mediated by an intracellular ERK signaling pathway associated with NMDARs.
纹状体被认为在控制自愿行为中起作用，且纹状体突触可塑性参与工具性学习。已知乙醇会改变突触可塑性，进而改变人类和动物的行为。然而，尚不清楚纹状体在乙醇对中枢神经系统的影响中是否起作用。本研究的目的是研究乙醇急性灌注对长时程增强（LTP）的影响，以阐明成瘾药物在纹状体中的作用机制。此外，我们研究了细胞内细胞外信号调节蛋白激酶（ERK）信号通路对皮质纹状体LTP诱导的作用。
采用细胞外记录技术，从大鼠背内侧纹状体（DMS）切片记录刺激诱发的群体峰电位（PS）。DMS切片中的LTP通过高频刺激（HFS）诱导。用蛋白质印迹技术评估DMS中的ERK水平。
ERK抑制剂U0126消除或显著减弱了DMS中HFS诱导的PS的LTP。N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂MK801和APV抑制纹状体LTP的诱导，并且在DMS中用MK801处理的切片中，HFS诱导的ERK激活降低。临床相关浓度的乙醇（22至88 mM）剂量依赖性地减弱了该脑区中HFS诱导的纹状体LTP和ERK激活。
DMS中PS的LTP至少部分由与NMDARs偶联的ERK途径介导。乙醇在该脑区以剂量依赖性方式减弱了HFS诱导的、ERK介导的LTP。这些结果表明，乙醇可能改变目标导向工具性动作学习基础的皮质纹状体回路的突触可塑性，这是由与NMDARs相关的细胞内ERK信号通路介导的。
