IMPROVEMENT OF MEMORY IN RODENTS BY THE SELECTIVE CB1 CANNABINOID RECEPTOR ANTAGONIST, SR-141716

Social short-term memory in rodents is based on the recognition of a j uvenile by an adult conspecific when the juvenile is presented on two successive occasions. Cannabimimetics are claimed to induce memory def icits in both humans and animals. In the brain, they mainly bind to CB 1 receptors for which anandamide is a purported endogenous ligand. SR 141716, a specific antagonist of CB1 receptors, dose-dependently rever ses biochemical and pharmacological effects of cannabimimetics. More p articularly, it antagonizes the inhibition of hippocampal long-term po tentiation induced by WIN 55,212-2 and anandamide, and it increases ar ousal when given alone. The present experiments study the ability of S R 141716 (from 0.03 to 3 mg/kg SC) to facilitate short-term olfactory memory in the social recognition test in rodents. SR 141716 improved s ocial recognition in a long intertrial paradigm with a threshold dose of 0.1 mg/kg SC. At 1 mg/kg, it antagonized the memory disturbance eli cited by retroactive inhibition. Scopolamine (0.06 mg/kg IP) partially reversed its memory-enhancing effect. Moreover, SR 141716 reduced mem ory deficit in aged rats (0.03-0.1 mg/kg) and mice (0.3-1 mg/kg). As S R 141716 is not known to exhibit any pharmacological activity which is not mediated by CB1 receptors, the results strongly support the conce pt that blockade of CB1 receptors plays an important role in consolida tion of short-term memory in rodents and suggest there may be a role f or an endogenous cannabinoid agonist tone (anandaminergic) in forgetti ng.