Clinical and preclinical evidence has indicated that estrogen depletion leads to memory impairments and increases the susceptibility to neural damage. Here, we have sought to investigate the effects of Cannabidiol (CBD) a non-psychotomimetic compound from Cannabis sativa, on memory deficits induced by estrogen depletion in rats, and its underlying mechanisms. Adult rats were subjected to bilateral ovariectomy, an established estrogen depletion model in rodents, or sham surgery and allowed to recover for three weeks. After that, they received daily injections of CBD (10 mg/kg) for fourteen days. Rats were tested in the inhibitory avoidance task, a type of emotionally-motivated memory. After behavioral testing they were euthanized, and their hippocampi were isolated for analysis of components of the Akt/GSK3β survival pathway and the antiapoptotic protein Bcl2. Results revealed that ovariectomy impaired avoidance memory, and CBD was able to completely reverse estrogen depletion-induced memory impairment. Ovariectomy also reduced Akt/GSK3β pathway’s activation by decreasing the phosphorylation levels of Akt and GSK3β and Bcl2 levels, which were ameliorated by CBD.

The present results indicate that CBD leads to a functional recovery accompanied by the Akt/GSK3β survival pathway’s activation, supporting its potential as a treatment for estrogen decline-induced deterioration of neural functioning and maintenance.

临床和临床前证据表明，雌激素消耗会导致记忆障碍并增加对神经损伤的易感性。在这里，我们试图研究大麻二酚 (CBD) 的作用，这是一种来自大麻的非拟精神病化合物，关于大鼠雌激素消耗引起的记忆缺陷及其潜在机制。成年大鼠接受双侧卵巢切除术，一种在啮齿动物中建立的雌激素耗竭模型，或假手术，并使其恢复三周。之后，他们每天注射 CBD（10 毫克/千克），持续 14 天。大鼠在抑制性回避任务中进行了测试，这是一种情绪驱动的记忆。在行为测试后，对它们实施安乐死，并分离它们的海马体，用于分析 Akt/GSK3β 存活途径和抗凋亡蛋白 Bcl2 的成分。结果表明，卵巢切除术损害了回避记忆，而 CBD 能够完全逆转雌激素消耗引起的记忆障碍。

目前的结果表明，CBD 导致伴随 Akt/GSK3β 存活途径激活的功能恢复，支持其作为治疗雌激素下降引起的神经功能和维持恶化的潜力。