Jin Peng, Yu Hai-Ling, Zhang Feng, Quan Zhe-Shan
Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, Yanbian University College of Pharmacy, Yanji 133000, PR China; Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Cancer Research Institute, College of Medicine, Seoul National University, Yongon-dong 28, Chongno-gu, Seoul 110-799, Republic of Korea; Department of Biomedical Science, Ischemic/Hypoxic Disease Institute, Cancer Research Institute, College of Medicine, Seoul National University, Yongon-dong 28, Chongno-gu, Seoul 110-799, Republic of Korea.
College of Medicine, Yanbian University, Park Street 977, Yanji, 133002 Jilin, PR China.
Pharmacol Biochem Behav. 2015 Jun;133:146-54. doi: 10.1016/j.pbb.2015.04.001. Epub 2015 Apr 10.
Oleoylethanolamide (OEA) is an endocannabinoid analog that belongs to a family of endogenous acylethanolamides. Increasing evidence suggests that OEA may act as an endogenous neuroprotective factor and participate in the control of mental disorder-related behaviors. In this study, we examined whether OEA is effective against depression and investigated the role of circulating endogenous acylethanolamides during stress. Mice were subjected to 28days of chronic unpredictable mild stress (CUMS), and during the last 21days, treated with oral OEA (1.5-6mg/kg) or 6mg/kg fluoxetine. Sucrose preference and open field test activity were used to evaluate depression-like behaviors during CUMS and after OEA treatment. Weights of the prefrontal cortex and hippocampus were determined, and the adrenal index was measured. Furthermore, changes in serum adrenocorticotropic hormone (ACTH), corticosterone (CORT) and total antioxidant capacity (T-AOC), brain-derived neurotrophic factor (BDNF), and lipid peroxidation product malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activities in the hippocampus and prefrontal cortex were detected. Our findings indicate that OEA normalized sucrose preferences, locomotion distances, rearing frequencies, prefrontal cortex and hippocampal atrophy, and adrenal indices. In addition, OEA reversed the abnormalities of BDNF and MDA levels and SOD activities in the hippocampus and prefrontal cortex, as well as changes in serum levels of ACTH, CORT, and T-AOC. The antidepressant effects of OEA may be related to the regulation of BDNF levels in the hippocampus and prefrontal cortex, antioxidant defenses, and normalizing hyperactivity in the hypothalamic-pituitary-adrenal axis (HPA).
油酰乙醇胺（OEA）是一种内源性大麻素类似物，属于内源性酰基乙醇胺家族。越来越多的证据表明，OEA可能作为一种内源性神经保护因子，参与精神障碍相关行为的调控。在本研究中，我们检测了OEA对抑郁症是否有效，并研究了应激期间循环内源性酰基乙醇胺的作用。将小鼠置于28天的慢性不可预测轻度应激（CUMS）环境中，在最后21天，给予口服OEA（1.5 - 6mg/kg）或6mg/kg氟西汀。采用蔗糖偏好试验和旷场试验活动来评估CUMS期间及OEA治疗后的抑郁样行为。测定前额叶皮质和海马的重量，并测量肾上腺指数。此外，检测血清促肾上腺皮质激素（ACTH）、皮质酮（CORT）和总抗氧化能力（T - AOC）、脑源性神经营养因子（BDNF）、脂质过氧化产物丙二醛（MDA）水平以及海马和前额叶皮质中超氧化物歧化酶（SOD）活性的变化。我们的研究结果表明，OEA使蔗糖偏好、运动距离、直立频率、前额叶皮质和海马萎缩以及肾上腺指数恢复正常。此外，OEA逆转了海马和前额叶皮质中BDNF和MDA水平以及SOD活性的异常，以及血清ACTH、CORT和T - AOC水平的变化。OEA的抗抑郁作用可能与调节海马和前额叶皮质中的BDNF水平、抗氧化防御以及使下丘脑 - 垂体 - 肾上腺轴（HPA）的功能亢进恢复正常有关。
