Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Deogyeong-daero, Giheung-gu, Yongin, 446-701, Republic of Korea.
Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 446-701, Republic of Korea.
Behav Brain Res. 2020 Feb 17;380:112439. doi: 10.1016/j.bbr.2019.112439. Epub 2019 Dec 17.
Chronic stress is depressogenic by altering neurotrophic and neuroinflammatory environments of the organism. The endocannabinoid system controls cognitive and emotional responses related with stress through the interaction with endocannabinoid receptors. β-Caryophyllene (BCP) is a CB2 agonist that exhibited anti-inflammatory, analgesic effects but minimal psychoactive effects. To test if BCP exhibits antidepressant-like action, animals were chronically restrained with additional stressors for 28 days, and BCP (25, 50, 100 mg/kg) was intraperitoneally injected once a day during the stress inflicting period. Then despair related behaviors and hippocampal expression of neurotrophic, inflammatory and cannabinoid receptor levels were measured. To test the effect of BCP on long-term depression, field potentials were measured during the application of lipopolysaccharide and low frequency stimulation. In the tail suspension test and forced swim test, chronic stress-induced despair behaviors were reduced by BCP. Also BCP improved the stress-related changes in the hippocampal expression of COX-2, BDNF, and CB2 receptor expression. In organotypic hippocampal slices, BCP reduced the lipopolysaccharide-induced intensification of the long-term depression. In conclusion, BCP improved chronic stress related behavioral and biochemical changes. These results suggest that BCP may be effective in treating depression and stress related mental illnesses.
慢性应激通过改变机体的神经营养和神经炎症环境来产生抑郁作用。内源性大麻素系统通过与内源性大麻素受体相互作用来控制与应激相关的认知和情绪反应。β-石竹烯（BCP）是一种 CB2 激动剂，具有抗炎、镇痛作用，但几乎没有精神活性作用。为了测试 BCP 是否具有抗抑郁样作用，将动物用额外的应激因素慢性束缚 28 天，并在施加应激期间每天腹膜内注射一次 BCP（25、50、100mg/kg）。然后测量与绝望相关的行为以及海马体中神经营养、炎症和大麻素受体水平的表达。为了测试 BCP 对长时程抑郁的影响，在应用脂多糖和低频刺激期间测量了场电位。在悬尾试验和强迫游泳试验中，BCP 减轻了慢性应激引起的绝望行为。BCP 还改善了海马体中 COX-2、BDNF 和 CB2 受体表达与应激相关的变化。在器官型海马切片中，BCP 降低了脂多糖诱导的长时程抑郁的增强。总之，BCP 改善了慢性应激相关的行为和生化变化。这些结果表明，BCP 可能对治疗抑郁和应激相关的精神疾病有效。
