BACKGROUND Stress is associated with relapse to alcohol seeking during abstinence, but the processes underlying this relationship are poorly understood. Noradrenaline is a key transmitter in stress responses and in stress-induced drug seeking. The alpha-1 adrenoceptor antagonist prazosin has been investigated as a treatment for alcoholism and for chronic stress disorders that are frequently comorbid with alcoholism. In rats, we previously showed that prazosin blocks reinstatement of alcohol seeking induced by footshock and yohimbine stressors and reduces yohimbine-induced brain activation. The role of alpha-1 adrenoceptors in reinstatement induced by other stressors is not known. Our most recent work is on the role of kappa opioid receptors in stress-induced reinstatement of alcohol seeking and have reported that the selective kappa opioid receptor agonist U50,488 induces reinstatement and neuronal activation in stress- and relapse-related brain regions. Here we determine the involvement of alpha-1 receptors in reinstatement and brain activation induced by U50,488. METHODS We trained male Long-Evans rats to self-administer alcohol (12% w/v), extinguished alcohol-reinforced responding, and then determined the effects of prazosin (1 mg/kg) on U50,488 (2.5 mg/kg)-induced reinstatement and regional Fos expression. RESULTS Prazosin blocked U50,488-induced reinstatement and decreased U50,488-induced Fos expression in the orbitofrontal cortex, nucleus accumbens core, ventral bed nucleus of the stria terminalis, central and basolateral amygdalar nuclei and ventral tegmental area. CONCLUSIONS These findings suggest that prazosin may reduce U50,488-induced relapse by inhibiting activity in 1 or more of these brain areas.

中文翻译：

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Alpha-1拮抗剂Prazosin对KOR激动剂诱导的饮酒恢复的影响。

背景技术压力与禁酒期间酒精寻觅的复发有关，但是这种关系的基础过程知之甚少。去甲肾上腺素是应激反应和应激诱导的药物寻找中的关键递质。已经研究了α-1肾上腺素能受体拮抗剂哌唑嗪作为酒精中毒和慢性酒精中毒的慢性应激障碍的治疗方法。在大鼠中，我们以前显示过哌唑嗪能抑制足部休克和育亨宾应激源诱导的寻求酒精的恢复，并减少育亨宾诱导的大脑激活。尚不知道α-1肾上腺素受体在其他应激源诱导的恢复中的作用。我们最近的工作是关于κ阿片受体在应激诱导的寻求酒精中的恢复作用，并且已经报道选择性κ阿片受体激动剂U50,488在与压力和复发相关的大脑区域中诱导了恢复和神经元活化。在这里，我们确定α1受体参与由U50,488诱导的恢复和大脑激活。方法我们训练了Long-Evans雄性大鼠自食酒精（12％w / v），消除了酒精增强的反应，然后测定了哌唑嗪（1 mg / kg）对U50,488（2.5 mg / kg）的影响诱导的恢复和区域Fos表达。结果Prazosin阻断了U50,488引起的恢复，并降低了U50,488引起的眶额叶皮质，伏隔核，纹状体腹侧腹核的Fos表达，中央和基底外侧杏仁核和腹侧被盖区。结论这些发现表明，哌唑嗪可通过抑制1个或多个这些大脑区域的活性来减少U50,488诱导的复发。