Solecki Wojciech, Krowka Tomasz, Kubik Jakub, Kaczmarek Leszek, Przewlocki Ryszard
Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Science, 12 Smetna Street, 31-343 Krakow, Poland.
Pharmacol Biochem Behav. 2008 Oct;90(4):512-6. doi: 10.1016/j.pbb.2008.03.031.
The proteins of Fos family are a potential candidate to link molecular mechanisms of morphine action with behavioural effects such as morphine-induced reward, dependence and tolerance. We used both male and female mice lacking fosB gene to study its contribution to morphine effects. Morphine analgesia (tail-flick test) and hypothermia were studied using morphine at cumulative doses in morphine-naive and morphine-tolerant (tolerance induced by 24 h prior 100 mg/kg morphine administration) mice. FosB -/- mice, as compared to fosB +/+ mice, developed enhanced tolerance to morphine-induced analgesia. No effects of genotype or gender on tolerance to morphine-induced hypothermia were observed. These results suggest that fosB may be involved in the development of tolerance to morphine analgesia but not hypothermia. The gender study implicates that lack of FosB proteins in female fosB -/- mice enhanced morphine analgesic potency. In conclusion, we show that fosB gene is important to analgesia but not hypothermia phenotype indicating its role in morphine effects.
Fos 家族蛋白是将吗啡作用的分子机制与诸如吗啡诱导的奖赏、依赖性和耐受性等行为效应联系起来的潜在候选者。我们使用缺乏 fosB 基因的雄性和雌性小鼠来研究其对吗啡效应的作用。在初次接触吗啡的小鼠和吗啡耐受小鼠（通过提前 24 小时给予 100 mg/kg 吗啡诱导耐受性）中，使用累积剂量的吗啡研究吗啡镇痛（甩尾试验）和体温过低情况。与 fosB +/+ 小鼠相比，fosB -/- 小鼠对吗啡诱导的镇痛产生了增强的耐受性。未观察到基因型或性别对吗啡诱导的体温过低耐受性有影响。这些结果表明，fosB 可能参与了对吗啡镇痛的耐受性发展，但不参与对体温过低的耐受性发展。性别研究表明，雌性 fosB -/- 小鼠中缺乏 FosB 蛋白增强了吗啡的镇痛效力。总之，我们表明 fosB 基因对镇痛很重要，但对体温过低表型不重要，这表明其在吗啡效应中的作用。
