McBride William J, Schultz Jonathan A, Kimpel Mark W, McClintick Jeanette N, Wang Mu, You Jinsam, Rodd Zachary A
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
Pharmacol Biochem Behav. 2009 Apr;92(2):304-13. doi: 10.1016/j.pbb.2008.12.019. Epub 2009 Jan 6.
The objective of this study was to determine the effects of ethanol injections on protein expression in the nucleus accumbens shell (ACB-sh) of alcohol-preferring (P), alcohol-non-preferring (NP) and Wistar (W) rats. Rats were injected for 5 consecutive days with either saline or 1 g/kg ethanol; 24 h after the last injection, rats were killed and brains obtained. Micro-punch samples of the ACB-sh were homogenized; extracted proteins were subjected to trypsin digestion and analyzed with a liquid chromatography-mass spectrometer procedure. Ethanol changed expression levels (1.15-fold or higher) of 128 proteins in NP rats, 22 proteins in P, and 28 proteins in W rats. Few of the changes observed with ethanol treatment for NP rats were observed for P and W rats. Many of the changes occurred in calcium-calmodulin signaling systems, G-protein signaling systems, synaptic structure and histones. Approximately half the changes observed in the ACB-sh of P rats were also observed for W rats. Overall, the results indicate a unique response to ethanol of the ACB-sh of NP rats compared to P and W rats; this unique response may reflect changes in neuronal function in the ACB-sh that could contribute to the low alcohol drinking behavior of the NP line.
本研究的目的是确定乙醇注射对嗜酒（P）、不嗜酒（NP）和Wistar（W）大鼠伏隔核壳（ACB-sh）中蛋白质表达的影响。大鼠连续5天注射生理盐水或1 g/kg乙醇；最后一次注射后24小时，处死大鼠并获取大脑。对ACB-sh的微量打孔样本进行匀浆；提取的蛋白质进行胰蛋白酶消化，并用液相色谱-质谱仪程序进行分析。乙醇改变了NP大鼠中128种蛋白质、P大鼠中22种蛋白质和W大鼠中28种蛋白质的表达水平（1.15倍或更高）。P和W大鼠中很少观察到乙醇处理对NP大鼠所产生的变化。许多变化发生在钙-钙调蛋白信号系统、G蛋白信号系统、突触结构和组蛋白中。在P大鼠的ACB-sh中观察到的变化中，约一半在W大鼠中也有观察到。总体而言，结果表明与P和W大鼠相比，NP大鼠的ACB-sh对乙醇有独特的反应；这种独特反应可能反映了ACB-sh中神经元功能的变化，这可能导致NP品系的低饮酒行为。
