The cannabinoid CB1 receptor has been shown to be critically involved in the extinction of fear memory. Systemic injection of a CB1 receptor antagonist prior to extinction training blocked extinction. Conversely, administration of the cannabinoid uptake inhibitor AM404 facilitated extinction in a dose-dependent manner. Here we show that bilateral infusion of CB1 receptor agonists into the amygd...

The intracellular mechanisms underlying memory reconsolidation critically involve cAMP signaling. These events were originally attributed to PKA activation by cAMP, but the identification of Exchange Protein Activated by cAMP (Epac), as a distinct mediator of cAMP signaling, suggests that cAMP-regulated processes that subserve memory reconsolidation are more complex. Here we investigated how ac...

Disrupting reconsolidation seems to be a promising approach to dampen the expression of fear memory. Recently, we demonstrated that disrupting reconsolidation by a pharmacological manipulation specifically targeted the emotional expression of memory (i.e., startle response). Here we test in a human differential fear-conditioning paradigm with fear-relevant stimuli whether the spacing of a singl...

The recent discovery by brain scientists of the reconsolidation of memory circuits (see research bibliography below) overturned the almost century-old tenet that emotional learnings and acquired responses maintained in long-term implicit memory are indelible—unerasable and permanent for the lifetime of the individual. Reconsolidation, induced endogenously through behavioral procedures, has been...

The retrieval of a consolidated, apparently stable memory can return it to a labile state, necessitating another period of stabilization, termed reconsolidation. During reconsolidation, memories are susceptible to modifications, thus providing the opportunity to change unwanted memories. In a test of whether the possibility to alter retrieved memories depends on the age of the memories, partici...

Therapies based on the impairment of reconsolidation or the enhancement of extinction offer the possibility of decreasing the persistent recollection of distressing memories. However, the direct interplay between reconsolidation and extinction has rarely been considered. Previously, we reported that reactivation induces reconsolidation of fear extinction memory. Here, using a step-down inhibito...

Ample evidence suggests that consolidated memories, upon their retrieval, enter a labile state, in which they might be susceptible to change. It has been proposed that memory labilization allows for the integration of relevant information in the established memory trace (memory updating). Memory labilization and reconsolidation do not necessarily occur when a memory is being reactivated, but on...

The reactivation of a memory can result in its destabilization, necessitating a process of memory reconsolidation to maintain its persistence. Here we show that the destabilization of a contextual fear memory is potentiated by the cannabinoid CB1 receptor agonist Arachidonyl-2-chloroethylamide (ACEA). Co-infusion of ACEA and the IkappaB kinase (IKK) inhibitor sulfasalazine (Sulf) into the dorsa...

On the morning of Monday, August 29, 2005, Hurricane Katrina made landfall in southeast Louisiana. The levee system of New Orleans failed catastrophically. Storm surges penetrated the entire city and lingered for weeks. Hurricane Katrina became known as one of the most intense, costliest, and deadliest natural disasters ever recorded in the history of the United States. Almost exactly 3 years l...

Upon recall, a memory can enter a labile state in which it requires new protein synthesis to restabilize. This two-phased reconsolidation process raises the prospect to directly target excessive fear memory as opposed to the formation of inhibitory memory following extinction training. In our previous studies, we convincingly demonstrated that 40 mg propranolol HCl administration before or afte...