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Long-term ethanol effects on acute stress responses: Modulation by dynorphin

机译:长期乙醇对急性应激反应的作用:强啡肽的调节

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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.
机译:脑部压力反应系统在成瘾过程中至关重要,它刺激了禁毒成瘾者的药物消耗和吸毒复发。同时,其功能会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消耗对大脑应激反应系统的影响的调节剂。使用两瓶选择范式,我们证明雄性强啡肽敲除小鼠中乙醇偏爱增强。暴露于轻度足部休克会增加野生型对照同窝仔动物的乙醇消耗,但强啡肽缺乏动物却没有。休克后5分钟测定的血液促肾上腺皮质激素水平不受基因型的影响。我们还使用边缘结构中的c-Fos免疫反应性确定了足部休克后的神经元反应性。这受到基因型和长期乙醇消耗的强烈影响。长期饮酒会增加野生型动物基底外侧杏仁核在足部休克诱导的c-Fos表达,但在强啡肽缺乏小鼠中却有相反的作用。在强啡肽敲除的脑室周围核,丘脑和海马中也发现了c-Fos反应性的改变。这些数据加在一起表明强啡肽在慢性乙醇暴露后在调节脑应激反应系统中起重要作用。

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