Prakash Anand, Zhang Huaibo, Pandey Subhash C
Department of Psychiatry, University of Illinois at Chicago, Jesse Brown VA Medical Center, Chicago, Illinois 60612, USA.
Alcohol Clin Exp Res. 2008 Jun;32(6):909-20. doi: 10.1111/j.1530-0277.2008.00650.x. Epub 2008 Apr 26.
Animal lines such as alcohol-preferring (P) and nonpreferring (NP) rats appear to be suitable animal models to investigate the biological basis of alcohol-drinking behaviors. The extended amygdala serves as a neuroanatomical substrate for alcohol-drinking behaviors. Brain-derived neurotrophic factor (BDNF) in the amygdala has been implicated in alcohol-drinking behaviors; however, its expression in the extended amygdala of P and NP rats is unknown. Therefore, we examined the basal expression of BDNF in the extended amygdala of alcohol naive P and NP rats.
We determined the basal mRNA and protein levels of BDNF by in situ RT-PCR and immuno-histochemical procedure, respectively, in the amygdaloid [central nucleus of amygdala (CeA), medial nucleus of amygdala (MeA), and basolateral amygdala (BLA)], nucleus accumbal (NAc shell and core), and bed nucleus of stria terminalis (BNST) [lateral BNST (lBNST), medial BNST (mBNST), and ventral BNST (vBNST)] brain structures of P and NP rats. In addition, we examined the localization of BDNF in neurons using double-immunofluorescence labeling of BDNF with neuron-specific nuclear protein (NeuN) and also determined the number of NeuN-positive neurons in the amygdaloid structures of P and NP rats.
The mRNA and protein levels of BDNF were found to be significantly lower in both the CeA and MeA, but not in the BLA, of P compared with NP rats. We also found that BDNF was expressed in neurons in the amygdaloid structures of P and NP rats. In addition, we found that the number of NeuN-positive neurons was similar in the amygdaloid structures of P and NP rats. Interestingly, the mRNA and protein levels of BDNF were also significantly lower in the lBNST, mBNST, and vBNST of P compared with NP rats. On the other hand, mRNA and protein levels of BDNF were similar in the NAc shell and core structures of P and NP rats.
P and NP rats are selectively bred for higher and lower alcohol preference, respectively; therefore it is possible that lower BDNF levels in the amygdaloid and BNST structures may be associated with the excessive alcohol-drinking behaviors of P rats.
诸如嗜酒（P）和不嗜酒（NP）大鼠等动物品系似乎是研究饮酒行为生物学基础的合适动物模型。扩展杏仁核是饮酒行为的神经解剖学基础。杏仁核中的脑源性神经营养因子（BDNF）与饮酒行为有关；然而，其在P和NP大鼠扩展杏仁核中的表达尚不清楚。因此，我们检测了未接触过酒精的P和NP大鼠扩展杏仁核中BDNF的基础表达。
我们分别通过原位逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法，测定了P和NP大鼠杏仁核[杏仁核中央核（CeA）、杏仁核内侧核（MeA）和杏仁核基底外侧核（BLA）]、伏隔核（NAc壳和核心）以及终纹床核（BNST）[外侧BNST（lBNST）、内侧BNST（mBNST）和腹侧BNST（vBNST）]脑区中BDNF的基础mRNA和蛋白水平。此外，我们使用BDNF与神经元特异性核蛋白（NeuN）的双重免疫荧光标记来检测BDNF在神经元中的定位，并确定P和NP大鼠杏仁核结构中NeuN阳性神经元的数量。
与NP大鼠相比，P大鼠的CeA和MeA中BDNF的mRNA和蛋白水平均显著降低，但BLA中未降低。我们还发现P和NP大鼠杏仁核结构中的神经元表达BDNF。此外，我们发现P和NP大鼠杏仁核结构中NeuN阳性神经元的数量相似。有趣的是，与NP大鼠相比，P大鼠的lBNST、mBNST和vBNST中BDNF的mRNA和蛋白水平也显著降低。另一方面，P和NP大鼠的NAc壳和核心结构中BDNF的mRNA和蛋白水平相似。
P和NP大鼠分别因对酒精的偏好较高和较低而进行选择性培育；因此，杏仁核和BNST结构中较低的BDNF水平可能与P大鼠的过度饮酒行为有关。
