Resumo

BACKGROUND: The endocannabinoid system (ECS) has several functions in the brain, including memory modulation. CB1 receptors are highly expressed in areas such as the dorsal hippocampus (HPC) known to be involved in long-term memory processing. The ECS, however, appears to be preferentially involved in aversively-motivated memories. Similarly, Glucocorticoids (GC) are released after an aversive situation and also modulate memories, and both, stress and dexamethasone (a synthetic glucocorticoid) promote endocannabinoids release. This study aims to evaluate the relationship between the ECS and GC in memory consolidation in the HPC. METHODS: Rats were trained in contextual fear conditioning task, using two protocols with different shock intensities (0.3 and 0.7mA) in order to control the level of aversiveness. The CB1 antagonist AM251 or its vehicle, were infused intra-hippocampus immediately after training. A stress session or dexamethasone injection were performed before the weak training protocol. RESULTS: AM251 infused into the HPC immediately after training was amnestic in the strong, but not in the weak protocol. In animals stressed before training in the weak protocol, AM251 was amnestic, reverting the stress facilitatory effect. Finally, animals receiving a dexamethasone i.p. injection before training presented a memory enhancement that was blocked by the post-training AM251 infusion. CONCLUSIONS: These findings suggest that a strong emotionally arousing experience is a necessary condition in order to recruit the ECS on memory consolidation. A stress event or, specifically, glucocorticoid could mimic the strong training protocol, and its further cannabinoid sensitivity by CB1 antagonist. This is the first demostration that the ECS interact with the GC in the hippocampus, suggesting a local GC-dependent ECS recruitment in order to modulate an aversive memory consolidation.