Cannabidiol (CBD) is a non-addictive ingredient of cannabis with antipsychotic potential, while ketamine (KET), an uncompetitive NMDA receptor inhibitor, has been extensively used as a psychotomimetic. Only few studies have focused on the role of CBD on the KET-induced motor profile, while no study has investigated the impact of CBD on KET-induced alterations in NMDA receptor subunit expression and ERK phosphorylation state, in brain regions related to the neurobiology and treatment of schizophrenia. Therefore, the aim of the present study is to evaluate the role of CBD on KET-induced motor response and relevant glutamatergic signaling in the prefrontal cortex, the nucleus accumbens, the dorsal and ventral hippocampus. The present study demonstrated that CBD pre-administration did not reverse ketamine-induced short-lasting hyperactivity, but it prolonged it over time. CBD alone decreased motor activity at the highest dose tested (30 mg/kg) while ketamine increased motor activity at the higher doses (30, 60 mg/kg). Moreover, KET induced regionally-dependent alterations in NR1 and NR2B expression and ERK phosphorylation that were reversed by CBD pre-administration. Interestingly, in the nucleus accumbens KET per se reduced NR2B and p-ERK levels, while the CBD/KET combination increased NR2B and p-ERK levels, as compared to control.

This study is the first to show that CBD prolongs KET-induced motor stimulation and restores KET-induced effects on glutamatergic signaling and neuroplasticity-related markers. These findings contribute to the understanding of CBD effects on the behavioral and neurobiological profiles of psychotogenic KET.

大麻二酚（CBD）是具有抗精神病潜力的大麻的非成瘾成分，而非竞争性NMDA受体抑制剂氯胺酮（KET）已被广泛用作拟精神病药物。只有很少的研究集中于CBD在KET诱导的运动模式中的作用，而没有研究研究CBD对KET诱导的与神经生物学和神经系统有关的大脑区域中NMDA受体亚基表达和ERK磷酸化状态变化的影响。精神分裂症的治疗。因此，本研究的目的是评估CBD在前额叶皮层，伏隔核，背侧和腹侧海马中，在KET诱导的运动反应和相关谷氨酸能信号传导中的作用。本研究表明，CBD的预先给药不能逆转氯胺酮引起的持续时间过长，但是随着时间的流逝，它延长了时间。单独的CBD在最高测试剂量（30 mg / kg）下会降低运动活动，而氯胺酮在较高剂量（30、60 mg / kg）下会增加运动活动。此外，KET诱导了NR1和NR2B表达以及ERK磷酸化的区域依赖性变化，这些变化可通过CBD预先给药逆转。有趣的是，与对照相比，伏隔核中KET本身降低了NR2B和p-ERK的水平，而CBD / KET组合则增加了NR2B和p-ERK的水平。

这项研究是第一个显示CBD延长KET诱导的运动刺激并恢复KET诱导的对谷氨酸能信号传导和神经可塑性相关标记的作用的研究。这些发现有助于了解CBD对精神病性KET的行为和神经生物学特征的影响。