Department of Psychology, School of Psychological Sciences, University of Haifa, Haifa 3498838, Israel.
The Integrated Brain and Behavior Research Center (IBBRC), University of Haifa, Haifa 3498838, Israel.
Int J Mol Sci. 2023 Jan 20;24(3):2052. doi: 10.3390/ijms24032052.
Cannabidiol (CBD) is a potential antidepressant agent. We examined the association between the antidepressant effects of CBD and alterations in brain microRNAs in the unpredictable chronic mild stress (UCMS) model for depression. UCMS male rats were injected with vehicle or CBD (10 mg/kg) and tested for immobility time in the forced swim test. Alterations in miRNAs (miR16, miR124, miR135a) and genes that encode for the 5HT1a receptor, the serotonergic transporter SERT, β-catenin, and CB1 were examined. UCMS increased immobility time in a forced swim test (i.e., depressive-like behavior) and altered the expression of miRNAs and mRNA in the ventromedial prefrontal cortex (vmPFC), raphe nucleus, and nucleus accumbens. Importantly, CBD restored UCMS-induced upregulation in miR-16 and miR-135 in the vmPFC as well as the increase in immobility time. CBD also restored the UCMS-induced decrease in htr1a, the gene that encodes for the serotonergic 5HT1a receptor; using a pharmacological approach, we found that the 5HT1a receptor antagonist WAY100135 blocked the antidepressant-like effect of CBD on immobility time. Our findings suggest that the antidepressant effects of CBD in a rat model for depression are associated with alterations in miR-16 and miR-135 in the vmPFC and are mediated by the 5HT1a receptor.
大麻二酚（CBD）是一种有潜力的抗抑郁药。我们研究了 CBD 的抗抑郁作用与慢性不可预测轻度应激（UCMS）抑郁模型中脑内 microRNAs 改变之间的关联。雄性 UCMS 大鼠给予载体或 CBD（10mg/kg）注射，并在强迫游泳试验中测试不动时间。检查了 microRNAs（miR16、miR124、miR135a）和编码 5HT1a 受体、5-羟色胺转运体 SERT、β-连环蛋白和 CB1 的基因的变化。UCMS 增加了强迫游泳试验中的不动时间（即抑郁样行为），并改变了腹侧前额叶皮质（vmPFC）、中缝核和伏隔核中 microRNAs 和 mRNA 的表达。重要的是，CBD 恢复了 UCMS 诱导的 vmPFC 中 miR-16 和 miR-135 的上调，以及不动时间的增加。CBD 还恢复了 UCMS 诱导的 htr1a 减少，htr1a 基因编码 5HT1a 受体；使用药理学方法，我们发现 5HT1a 受体拮抗剂 WAY100135 阻断了 CBD 对不动时间的抗抑郁作用。我们的研究结果表明，CBD 在抑郁大鼠模型中的抗抑郁作用与 vmPFC 中 miR-16 和 miR-135 的改变有关，并由 5HT1a 受体介导。
