title: Antidepressant-like effects of oleoylethanolamide in a mouse model of chronic unpredictable mild stress.
abstract: 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).
authors: 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.
authors: Peng
authors: P
authors: Jin
authors: College of Medicine, Yanbian University, Park Street 977, Yanji, 133002 Jilin, PR China. Electronic address: hlyu@ybu.edu.cn.
authors: Hai-Ling
authors: HL
authors: Yu
authors: College of Medicine, Yanbian University, Park Street 977, Yanji, 133002 Jilin, PR China.
authors: Tian-Lan
authors: College of Medicine, Yanbian University, Park Street 977, Yanji, 133002 Jilin, PR China.
authors: Feng
authors: F
authors: Zhang
authors: 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. Electronic address: zsquan@ybu.edu.cn.
authors: Zhe-Shan
authors: ZS
authors: Quan
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D001284:Atrophy / Q000188:drug therapy; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000494:pharmacology* / Q000627:therapeutic use*; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009829:Oleic Acids / Q000494:pharmacology* / Q000627:therapeutic use*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013315:Stress, Psychological / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D063388:Endocannabinoids; D009829:Oleic Acids; D005473:Fluoxetine; C488250:oleoylethanolamide; D008315:Malondialdehyde; D000324:Adrenocorticotropic Hormone; D013482:Superoxide Dismutase; D003345:Corticosterone
keywords: Antidepressant; Brain-derived neurotrophic factor; HPA; Mice; Oleoylethanolamide; Oxidative stress