Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.
Addict Biol. 2013 Jul;18(4):678-88. doi: 10.1111/j.1369-1600.2012.00494.x. Epub 2012 Sep 21.
The brain stress-response system is critically involved in the addiction process, stimulating drug consumption and the relapse to drug taking in abstinent addicts. At the same time, its functioning is affected by chronic drug exposure. Here, we have investigated the role of the endogenous opioid peptide dynorphin as a modulator of effects of long-term ethanol consumption on the brain stress-response system. Using the two-bottle choice paradigm, we demonstrate an enhanced ethanol preference in male dynorphin knockout mice. Exposure to mild foot shock increased ethanol consumption in wild-type control littermates, but not in dynorphin-deficient animals. Blood adrenocorticotropic hormone levels determined 5 minutes after the shock were not affected by the genotype. We also determined the neuronal reactivity after foot shock exposure using c-Fos immunoreactivity in limbic structures. This was strongly influenced by both genotype and chronic ethanol consumption. Long-term alcohol exposure elevated the foot shock-induced c-Fos expression in the basolateral amygdala in wild-type animals, but had the opposite effect in dynorphin-deficient mice. An altered c-Fos reactivity was also found in the periventricular nucleus, the thalamus and the hippocampus of dynorphin knockouts. Together these data suggest that dynorphin plays an important role in the modulation of the brain stress-response systems after chronic ethanol exposure.
大脑应激反应系统在成瘾过程中起着至关重要的作用，它刺激药物消费，并促使戒除毒瘾的人重新开始吸毒。与此同时，其功能也受到慢性药物暴露的影响。在这里，我们研究了内源性阿片肽强啡肽作为长期乙醇摄入对大脑应激反应系统影响的调节剂的作用。使用两瓶选择范式，我们证明了雄性强啡肽敲除小鼠对乙醇的偏好增强。在野生型对照同窝仔中，轻度足部电击会增加乙醇的摄取量，但在缺乏强啡肽的动物中则不会。电击后 5 分钟测定的血液促肾上腺皮质激素水平不受基因型影响。我们还使用边缘结构中的 c-Fos 免疫反应性来确定足部电击暴露后的神经元反应性。这受到基因型和慢性乙醇摄入的强烈影响。长期酒精暴露会增加野生型动物中杏仁基底外侧核中足部电击引起的 c-Fos 表达，但在强啡肽缺乏的小鼠中则有相反的效果。在强啡肽敲除小鼠的室旁核、丘脑和海马体中也发现了改变的 c-Fos 反应性。这些数据表明，强啡肽在慢性乙醇暴露后对大脑应激反应系统的调节中起着重要作用。
