Department of Pharmacology, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran.
Razi Drug Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Jul;397(7):5029-5047. doi: 10.1007/s00210-023-02941-4. Epub 2024 Jan 8.
Cognitive disorders are associated with valproate and drugs used to treat neuropsychological diseases. Cannabidiol (CBD) has beneficial effects on cognitive function. This study examined the effects of co-administration of CBD and valproate on memory consolidation, cholinergic transmission, and cyclic AMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling pathway in the prefrontal cortex (PFC) and hippocampus (HPC).
One-trial, step-through inhibitory test was used to evaluate memory consolidation in rats. The intra-CA1 injection of physostigmine and atropine was performed to assess the role of cholinergic transmission in this co-administration. Phosphorylated CREB (p-CREB)/CREB ratio and BDNF levels in the PFC and HPC were evaluated.
Post-training intraperitoneal (i.p.) valproate injection reduced memory consolidation; however, post-training co-administration of CBD with valproate ameliorated memory impairment induced by valproate. Post-training intra-CA1 injection of physostigmine at the ineffective doses in memory consolidation (0.5 and 1 µg/rat), plus injection of 10 mg/kg of CBD as an ineffective dose, improved memory loss induced by valproate, which was associated with BDNF and p-CREB level enhancement in the PFC and HPC. Conversely, post-training intra-CA1 injection of ineffective doses of atropine (1 and 2 µg/rat) reduced the positive effects of injection of CBD at a dose of 20 mg/kg on valproate-induced memory loss associated with BDNF and p-CREB level reduction in the PFC and HPC.
The results indicated a beneficial interplay between valproate and CBD in the process of memory consolidation, which probably creates this interaction through the BDNF-CREB signaling pathways in the cholinergic transmission of the PFC and HPC regions.
认知障碍与丙戊酸和治疗神经心理疾病的药物有关。大麻二酚（CBD）对认知功能有有益的影响。本研究检查了 CBD 和丙戊酸联合给药对前额叶皮层（PFC）和海马（HPC）中记忆巩固、胆碱能传递以及环腺苷酸反应元件结合蛋白（CREB）-脑源性神经营养因子（BDNF）信号通路的影响。
使用单次试验、跨步抑制试验评估大鼠的记忆巩固。通过 CA1 内注射石杉碱甲和阿托品来评估胆碱能传递在此联合给药中的作用。评估 PFC 和 HPC 中的磷酸化 CREB（p-CREB）/CREB 比值和 BDNF 水平。
丙戊酸钠腹腔注射后可降低记忆巩固；然而，丙戊酸钠联合 CBD 给药可改善丙戊酸钠引起的记忆障碍。在记忆巩固（0.5 和 1μg/大鼠）无效剂量的 CA1 内注射石杉碱甲，再加上 CBD（20mg/kg）无效剂量的注射，可改善丙戊酸钠引起的记忆丧失，这与 PFC 和 HPC 中 BDNF 和 p-CREB 水平的增强有关。相反，在 CA1 内注射无效剂量的阿托品（1 和 2μg/大鼠）可降低 CBD（20mg/kg）剂量对丙戊酸钠引起的记忆丧失的积极作用，这与 PFC 和 HPC 中 BDNF 和 p-CREB 水平的降低有关。
这些结果表明丙戊酸和 CBD 之间在记忆巩固过程中存在有益的相互作用，这可能是通过 PFC 和 HPC 区域的胆碱能传递中的 BDNF-CREB 信号通路产生这种相互作用的。
