Department of Psychiatry, University of Illinois at Chicago and Jesse Brown VA Medical Center, 820 S. Damen Avenue (M/C 151). Chicago, IL 60612, USA.
Addict Biol. 2011 Apr;16(2):238-50. doi: 10.1111/j.1369-1600.2010.00275.x. Epub 2010 Dec 23.
Innate anxiety appears to be a robust factor in the promotion of alcohol intake, possibly due to the anxiolytic effects of self-medication with alcohol. Brain-derived neurotrophic factor (BDNF) and its downstream target, activity-regulated cytoskeleton-associated (Arc) protein, play a role in the regulation of synaptic function and structure. In order to examine the role of the BDNF-Arc system and associated dendritic spines in the anxiolytic effects of ethanol, we investigated the effects of acute ethanol exposure on anxiety-like behaviors of alcohol-preferring (P) and -nonpreferring (NP) rats. We also examined changes in the expression of BDNF and Arc, and dendritic spine density (DSD), in amygdaloid brain regions of P and NP rats with or without ethanol exposure. It was found that in comparison with NP rats, P rats displayed innate anxiety-like behaviors, and had lower mRNA and protein levels of both BDNF and Arc, and also had lower DSD in the central amygdala (CeA) and medial amygdala (MeA), but not in the basolateral amygdala (BLA). Acute ethanol treatment had an anxiolytic effect in P, but not in NP rats, and was associated with an increase in mRNA and protein levels of BDNF and Arc, and in DSD in the CeA and MeA, but not BLA. These results suggest that innate deficits in BDNF-Arc levels, and DSD, in the CeA and MeA may be involved in the anxiety-like and excessive alcohol-drinking behaviors of P rats, as ethanol increased these amygdaloid synaptic markers and produced anxiolytic effects in P rats, but not NP rats.
先天焦虑似乎是促进酒精摄入的一个强有力因素，这可能是由于酒精自我给药的抗焦虑作用。脑源性神经营养因子 (BDNF) 及其下游靶标，活性调节细胞骨架相关蛋白 (Arc)，在调节突触功能和结构中发挥作用。为了研究 BDNF-Arc 系统及其相关树突棘在乙醇抗焦虑作用中的作用，我们研究了急性乙醇暴露对酒精偏好 (P) 和非偏好 (NP) 大鼠焦虑样行为的影响。我们还研究了 P 和 NP 大鼠在有无乙醇暴露的情况下，杏仁核脑区 BDNF 和 Arc 的表达变化，以及树突棘密度 (DSD)。结果发现，与 NP 大鼠相比，P 大鼠表现出先天的焦虑样行为，BDNF 和 Arc 的 mRNA 和蛋白水平均较低，并且在中央杏仁核 (CeA) 和内侧杏仁核 (MeA) 中的 DSD 也较低，但在基底外侧杏仁核 (BLA) 中则没有。急性乙醇处理对 P 大鼠有抗焦虑作用，但对 NP 大鼠没有，这与 CeA 和 MeA 中的 BDNF 和 Arc 的 mRNA 和蛋白水平增加以及 DSD 增加有关，但 BLA 没有。这些结果表明，CeA 和 MeA 中先天的 BDNF-Arc 水平和 DSD 缺陷可能与 P 大鼠的焦虑样和过度饮酒行为有关，因为乙醇增加了这些杏仁核突触标志物，并对 P 大鼠产生了抗焦虑作用，但对 NP 大鼠没有。
