Consolidation of memory after its reactivation: involvement of beta noradrenergic receptors in the late phase.

Evidence is growing that the cAMP pathway through the cAMP responsive element binding protein (CREB) transcription factor plays an important role in long-term memory formation (LTM). To study the role of beta-noradrenergic receptors, positively linked to the cAMP second-messenger system, in the dynamics of LTM processes, we used a memory-reactivation paradigm because recent studies in our laboratory confirmed that reactivated memory is labile and undergoes an extended reconsolidation process. In an eight-arm maze, rats were trained to choose the same three baited arms; 24 hr later, memory was reactivated and then the rats were injected intracerebroventricularly at 5 min, 30 min, 60 min, or 5 hr later with the beta-antagonist timolol or with saline. The results showed that injection of timolol induced amnesia only at the 60 min post-reactivation interval, whereas all control groups and groups that were timolol-injected at other post-reactivation intervals displayed optimal retention. The delayed amnesic action of timolol suggests that beta noradrenergic receptors and the cAMP cascade are implicated in the late phase of reprocessing of a remembered event.