School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
J Neurochem. 2010 Aug;114(4):1168-76. doi: 10.1111/j.1471-4159.2010.06844.x. Epub 2010 Jun 1.
The key neurochemical systems and structures involved in the predisposition to substance abuse and preference to ethanol (EtOH) are not known in detail but clearly dopamine (DA) is an important modulator of addiction. Recent data indicate that alpha-synuclein (alpha-syn), a pre-synaptic protein, plays a role in regulation of DA release from the pre-synaptic terminals in striatum and the expression of this protein is different after drug abuse or following abstinence. In the present work, we analysed stimulated DA overflow in the dorsal and ventral striatum in EtOH naïve alko alchohol (AA) and alko non-alchohol (ANA) rats selected for more than 100 generations for their differential EtOH preference. In the same structures, we studied the expression of alpha-syn using western blotting. AA rats, in comparison with ANA rats, showed a marked reduction of stimulated peak DA overflow and higher levels of alpha-syn in the nucleus accumbens core. In the same structure, DA re-uptake was increased in AA rats in comparison with ANA rats. The effects of EtOH at low (0.1 g/kg) and higher (3 mg/kg) doses on DA overflow measured in the nucleus accumbens shell were similar in both lines. These results indicate that high expression of alpha-syn may contribute to the reduced DA overflow and the possible activation of re-uptake in the nucleus accumbens core of AA rats in comparison with ANA rats.
在物质滥用和对乙醇（EtOH）偏好的倾向中涉及的关键神经化学系统和结构尚不清楚，但多巴胺（DA）显然是成瘾的重要调节剂。最近的数据表明，α-突触核蛋白（α-syn），一种前突触蛋白，在调节纹状体中来自前突触末梢的 DA 释放和该蛋白在滥用药物或戒断后的表达中起作用。在本工作中，我们分析了在 EtOH -naive alko 酒精（AA）和 alko 非酒精（ANA）大鼠的背侧和腹侧纹状体中刺激的 DA 溢出，这些大鼠经过 100 多代的选择，对 EtOH 有不同的偏好。在相同的结构中，我们使用 Western blot 研究了 α-syn 的表达。与 ANA 大鼠相比，AA 大鼠表现出刺激峰 DA 溢出的明显减少和伏隔核核心中 α-syn 的更高水平。在相同的结构中，AA 大鼠的 DA 再摄取比 ANA 大鼠增加。在两种品系中，低（0.1 g/kg）和高（3 mg/kg）剂量 EtOH 对伏隔核壳中 DA 溢出的影响相似。这些结果表明，高表达的 α-syn 可能有助于减少 AA 大鼠与 ANA 大鼠相比，伏隔核核心中的 DA 溢出和可能的再摄取激活。
