Research Foundation Itsuu Laboratory, 2-28-10 Tamagawa, Setagaya-ku, Tokyo 158-0094, Japan.
Pharmacol Biochem Behav. 2013 Mar;104:1-9. doi: 10.1016/j.pbb.2013.01.008. Epub 2013 Jan 17.
Am80 is a synthetic retinoid that has been used clinically for patients with acute promyelocytic leukemia and has been reported to affect the brain and its neurons. We investigated the influence of Am80 on anti-anxiety-like behavior, which is a characteristic of age-associated emotional disorder, in the P8 strain of senescence-accelerated mice (SAMP8). Am80 at a concentration of 2 mg/kg/day was administered to the mice in their feed for 1.5 months. In open-field and hole-board tests, the number of ambulation, rearing, and head dipping actions, as well as the distance moved were significantly decreased in Am80-treated SAMP8 compared with untreated SAMP8. In the light/dark box test, the latencies for the first exit were significantly increased in the Am80-treated SAMP8 compared with the untreated SAMP8. Immunohistochemical analysis revealed that the area of serotonin transporter-positive immunoreactivity in the coronal sections of the forebrain of the Am80-treated SAMP8 was increased compared with the untreated SAMP8. Furthermore, the metabolic turnovers of serotonin and dopamine were increased in the amygdalae of the SAMP8 by Am80 treatment. Thus, in the present study, Am80 was found to improve exploratory and emotional behavior in SAMP8, suggesting that Am80 regulates monoamines directly or indirectly in this senescence-accelerated model.
Am80 是一种合成维甲酸，已在临床上用于治疗急性早幼粒细胞白血病，并已报道其对大脑及其神经元有影响。我们研究了 Am80 对 P8 品系快速老化小鼠（SAMP8）焦虑样行为的影响，焦虑样行为是与年龄相关的情绪障碍的特征之一。Am80 以 2mg/kg/天的浓度添加到饲料中，连续给 SAMP8 小鼠喂食 1.5 个月。在旷场和洞板试验中，与未处理的 SAMP8 相比，Am80 处理的 SAMP8 中走动、竖起和头浸动作的次数以及移动的距离明显减少。在明暗箱试验中，与未处理的 SAMP8 相比，Am80 处理的 SAMP8 中首次出口的潜伏期显著增加。免疫组织化学分析显示，与未处理的 SAMP8 相比，Am80 处理的 SAMP8 前额叶冠状切片中血清素转运蛋白阳性反应的面积增加。此外，Am80 处理增加了 SAMP8 杏仁核中血清素和多巴胺的代谢周转率。因此，在本研究中，发现 Am80 改善了 SAMP8 的探索和情绪行为，表明 Am80 直接或间接调节这种加速衰老模型中的单胺类物质。
