Läck A K, Christian D T, Diaz M R, McCool B A
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Alcohol. 2009 Feb;43(1):25-33. doi: 10.1016/j.alcohol.2008.11.002.
Withdrawal (WD) anxiety is a significant factor contributing to continued alcohol abuse in alcoholics. This anxiety is extensive, long-lasting, and develops well after the obvious physical symptoms of acute WD. The neurobiological mechanisms underlying this prolonged WD-induced anxiety are not well understood. The basolateral amygdala (BLA) is a major emotional center in the brain and regulates the expression of anxiety. New evidence suggests that increased glutamatergic function in the BLA may contribute to WD-related anxiety following chronic ethanol exposure. Recent evidence also suggests that kainate-type ionotropic glutamate receptors are inhibited by intoxicating concentrations of acute ethanol. This acute sensitivity suggests potential (KA-R) contributions by these receptors to the increased glutamatergic function seen during chronic exposure. Therefore, we examined the effect of chronic intermittent ethanol (CIE) and WD on KA-R-mediated synaptic transmission in the BLA of Sprague-Dawley rats. Our study showed that CIE, but not WD, increased synaptic responses mediated by KA-Rs. Interestingly, both CIE and WD occluded KA-R-mediated synaptic plasticity. Finally, we found that BLA field excitatory postsynaptic potential responses were increased during CIE and WD via a mechanism that is independent of glutamate release from presynaptic terminals. Taken together, these data suggest that KA-Rs might contribute to postsynaptic increases in glutamatergic synaptic transmission during CIE and that the mechanisms responsible for the expression of KA-R-dependent synaptic plasticity might be engaged by chronic ethanol exposure and WD.
戒断（WD）焦虑是导致酗酒者持续酗酒的一个重要因素。这种焦虑广泛、持久，且在急性WD明显的身体症状出现很久之后才会产生。这种长期由WD引发的焦虑背后的神经生物学机制尚未完全明了。基底外侧杏仁核（BLA）是大脑中的一个主要情绪中枢，可调节焦虑的表达。新证据表明，BLA中谷氨酸能功能增强可能导致慢性乙醇暴露后与WD相关的焦虑。最近的证据还表明，急性乙醇中毒浓度可抑制海人藻酸型离子型谷氨酸受体。这种急性敏感性表明这些受体可能对慢性暴露期间谷氨酸能功能增强有潜在贡献（KA-R）。因此，我们研究了慢性间歇性乙醇（CIE）和WD对Sprague-Dawley大鼠BLA中海人藻酸受体（KA-R）介导的突触传递的影响。我们的研究表明，CIE而非WD增加了KA-R介导的突触反应。有趣的是，CIE和WD都阻断了KA-R介导的突触可塑性。最后，我们发现，在CIE和WD期间，BLA场兴奋性突触后电位反应通过一种独立于突触前终末谷氨酸释放的机制而增加。综上所述，这些数据表明，KA-R可能在CIE期间对谷氨酸能突触传递的突触后增强有贡献，并且KA-R依赖性突触可塑性表达的相关机制可能因慢性乙醇暴露和WD而激活。
