Systemic administration of cannabinoid agonists impairs cerebellum-dependent motor learning. The cannabinoid-induced impairment of motor learning has been hypothesized to be due to disruption of Purkinje cell plasticity within the cerebellar cortex. In the current study, we tested this hypothesis in rats with localized microinfusions of cannabinoid agonists and antagonists into the cerebellar cortex during eyeblink conditioning, a type of cerebellum-dependent motor learning. Infusions of the cannabinoid agonists WIN55,212-2 or ACEA directly into the eyeblink conditioning microzone of the cerebellar cortex severely impaired acquisition of eyeblink conditioning, whereas the CB1R antagonist SR141716A did not produce a significant impairment. Infusions of WIN55,212-2 outside of the eyeblink conditioning microzone did not impair motor learning, establishing anatomical specificity for the agonist effects. The motor learning impairment caused by WIN55,212-2 and ACEA was rescued by SR141716A, indicating that the learning deficit was produced through CB1Rs. The current findings demonstrate that the effects of cannabinoid receptor agonists on motor learning are localized to CB1Rs within a discrete microzone of the cerebellar cortex.

中文翻译：

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小脑皮质内的大麻素激动剂给药会损害运动学习能力。

大麻素激动剂的系统性给药会损害小脑依赖的运动学习。假设大麻素诱导的运动学习障碍是由于小脑皮层内Purkinje细胞可塑性的破坏。在当前的研究中，我们在眨眼调节（一种依赖于小脑的运动学习）中，将大麻素激动剂和拮抗剂局部微输注到小脑皮层中，对这一假设进行了测试。将大麻素激动剂WIN55,212-2或ACEA直接输注到小脑皮层的眨眼调节微区会严重损害眨眼调节的获得，而CB1R拮抗剂SR141716A不会产生明显的损害。在眨眼条件微区外部注入WIN55,212-2不会损害运动学习，建立激动剂作用的解剖学特异性。SR141716A挽救了由WIN55,212-2和ACEA引起的运动学习障碍，这表明学习缺陷是通过CB1R产生的。目前的发现表明，大麻素受体激动剂对运动学习的影响局限于小脑皮质离散微区内的CB1Rs。