抄録
Cannabinoids exert their psychomotor actions through cannabinoid CB1 receptor in the brain. Genetic deletion of CB1 in mice causes various symptoms including change in locomotor activity, increased ring catalepsy, hippocampal plasticity, and impaired extinction of hippocampus-dependent learning. Although the cerebellar cortex contains the highest level of CB1 in the brain, cerebellum-related functional deficits have not been reported in CB1 knockout mice. To elucidate the roles of CB1 in cerebellar function, we subjected CB1 knockout mice to a delay version of classical eyeblink conditioning. We found that memory formation of delay eyeblink conditioning was severely impaired in CB1 knockout mice. In contrast, they exhibited normal performance in a trace version of eyeblink conditioning with 500-ms stimulus free interval intervened between the CS offset and the US onset, which is regarded as a hippocampus-dependent associative learning. We also found that intraperitoneal injection of the CB1 antagonist SR141716A (rimonabant) to wild-type mice caused severe impairment in acquisition but not extinction of the delay eyeblink conditioning. SR141716A treatment had no effect on the trace eyeblink conditioning with 500-ms or 750-ms trace interval. These results indicate that endogenous cannabioid signaling through CB1 is essential for cerebellum-dependent discrete motor learning especially for its acquisition phase. [J Physiol Sci. 2007;57 Suppl:S72]
