Effects of cannabinoids on the short and long-term memory functions in mice

Abstract

Evidence from rodent studies support the view that agonists of cannabinoid CB1 receptors impair tasks that involve memory, while CB1antagonists improve performance on such tasks. However, any one behavioural procedure to assess memory is open to influences from a variety of non-memory sources, including motivation, attention, arousal, and motor processes. To be confident of interpreting the effects of drugs on such tasks as being due to memory requires convergence of evidence from a variety of procedures that differ in motivation, attention, arousal and response requirements, but share a common reliance on memory. The purpose of the present study was to determine the effects of the CB1 agonist, CP55940, and the antagonist, SR14716A, in the8-arm radial maze. 36 male C57BL/6J mice were trained to a criterion of =60% correct entries for two consecutive trials. Mice were treated with cannabinoid agonist and antagonist in a fully-balanced within-subjects design and tested in the maze. Long-term (reference memory) and short-term memory (working memory) were assessed by measuring the number of correct entries, working memory errors and reference memory errors in the 8-arm radial maze apparatus. CP55940 caused a significant deficit on long-term memory, as shown by a decrease in percent correct entries and an increase in entries into never-baited arms. SR141716A reversed the effect of CP55940 on these measures. CP55940 also increased the number of entries into previously baited arms (working memory error), which was not affected by SR141716A. SR141716A had no significant effects on its own on any measure of memory. The present study shows that cannabinoid CB1 receptors do play an important role in reference memory. While the CB1 agonist did impair working memory, this effect was apparently not mediated by CB1 receptors as SR141716Adid not attenuate the effect.