Blockade of cannabinoid CB1 receptors alters contextual learning and memory

The endocannabinoid system appears to have an important role in specific aspects of learning and memory, yet there has been no systematic study of the role of cannabinoid receptors in contextual fear conditioning. The present study examined the effects of cannabinoid CB1 receptor blockade on the acquisition, consolidation, and expression of contextual fear using the selective cannabinoid CB1 receptor antagonist AM251. AM251 produced a decrease in the expression of contextual fear when administered prior to training, testing, or both. This effect was observed when footshock was signaled by an auditory cue but not in an unsignaled shock version of the task. Moreover, blocking cannabinoid CB1 receptors had no effect on consolidation of contextual memory regardless of the conditioning paradigm. These data indicate that inhibition of cannabinoid CB1 receptors produces specific deficits in processing contextual information and that the effects of CB1 antagonists on contextual learning may differ from effects on other types of learning.