Cannabinoid modulation of memory consolidation within the cerebellum

Cannabinoid receptors contribute to learning and synaptic plasticity mechanisms. The cerebellum contains a high density of cannabinoid receptors and manipulations of cannabinoid receptors affect synaptic plasticity within the cerebellar cortex. In vivo studies have found that cannabinoid agonists impair learning of cerebellum-dependent eyeblink conditioning in rodents and humans. However, the role of cannabinoid receptors or endocannabinoids in memory consolidation within the cerebellum has not been examined. In the current study, we examined the role of cannabinoid receptors and endocannabinoids during learning and consolidation of eyeblink conditioning in rats. Administration of the cannabinoid receptor agonist WIN55,212-2 or drugs that increase/decrease endocannabinoid levels directly into the cerebellar cortex before each training session resulted in marked learning impairments. When administered 1 h after each training session, during memory consolidation, the cannabinoid inverse agonist SR141716A or the endocannabinoid suppressor THL impaired memory. In contrast, increasing endocannabinoid levels with JZL-184 or infusion of WIN55,212-2 within the cerebellar cortex facilitated memory consolidation 1h post-training. Intracerebellar manipulations of cannabinoid receptors or endocannabinoid levels had no effect on memory consolidation when administered 3 or 6h after each training session. The results demonstrate that cannabinoids impair cerebellar learning, but facilitate memory consolidation mechanisms within the cerebellar cortex 1-3h after training.