Cannabidiolic acid methyl ester (HU-580) is a more stable compound than cannabidiolic acid (CBDA) which has been shown to be effective in reducing nausea, anxiety, depression behaviors in animal models. Here we extend the investigation of this compound to determine its effect on the sleep-wake cycle in male Wistar rats. HU-580 dose-dependently (0.1, 1.0 or 100 μg/Kg, i.p.) prolonged wakefulness (W) and decreased slow wave sleep (SWS) duration whereas rapid eye movement sleep (REMS) showed no statistical change. In addition, the brain microdialysis probes either placed at nucleus accumbens (NAc) or into the basal forebrain in freely moving animals were used to evaluate the effects of HU-580 treatment on neurotransmitters related to the sleep-wake cycle modulation. HU-580 enhanced extracellular levels of dopamine, serotonin collected from NAc while adenosine and acetylcholine were increased in basal forebrain. In summary, HU-580 seems to possess wake-promoting pharmacological properties and enhances the levels of wake-related neurochemicals. This is the first report of effects of HU-580 on sleep modulation expanding the very limited existent data on the neurobiological effects of HU-580 on rats.

中文翻译：

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大麻二酚甲酯对大鼠的睡眠和神经化学调节作用。

大麻二酸甲酯（HU-580）是比大麻二酸（CBDA）更稳定的化合物，后者已被证明可有效减少动物模型中的恶心，焦虑和抑郁行为。在这里，我们扩展了对这种化合物的研究，以确定其对雄性Wistar大鼠睡眠-觉醒周期的影响。HU-580剂量依赖性（0.1、1.0或100μg/ Kg，ip）可以延长清醒时间（W），并减少慢波睡眠（SWS）的持续时间，而快速眼动睡眠（REMS）则无统计学变化。此外，将脑微透析探针放置在自由移动动物的伏伏核（NAc）或基底前脑中，用于评估HU-580治疗对与睡眠-觉醒周期调节有关的神经递质的影响。HU-580增强了细胞内多巴胺水平，在基础前脑中，从NAc收集5-羟色胺，而腺苷和乙酰胆碱增加。总之，HU-580似乎具有促进唤醒的药理特性，并增强了与唤醒相关的神经化学物质的水平。这是HU-580对睡眠调节作用的首次报道，扩大了关于HU-580对大鼠神经生物学作用的非常有限的现有数据。