Le blocage de la consolidation et de la reconsolidation des souvenirs émotionnels chez l'humain à l'aide du propranolol

A recent theory of memory proposes that when a well-consolidated memory is reactivated, it becomes labile again and susceptible to change before being restabilized (reconsolidated) in long-term memory. This new memory theory refutes the classical model of consolidation, which suggests that once consolidated, memories are permanent and hence resistant to the effects of amnestic agents. Studies validating reconsolidation theory in animals abound, but fewer studies have been conducted in humans. The objective of the current thesis is to verify the potential of the pharmacological agent propranolol (a β-blocker) to impair newly acquired or already consolidated emotional memories in healthy subjects and subjects suffering from posttraumatic stress disorder (PTSD). We conducted a double blind controlled trial where propranolol (vs. placebo) was administered to healthy subjects during the acquisition of a new memory (an emotionally valenced story) and one week later, during its reactivation. The aim of the first paper was to evaluate the efficacy of propranolol to reduce the consolidation and reconsolidation of emotional memories. Furthermore, since animal studies have shown that these two memory processes occur within a given time window, the timing of the propranolol administration was taken into consideration. The results showed that propranolol was able to dampen the consolidation and reconsolidation of an emotional story as evidenced by a lower percentage of correct answers at recall compared to the control group. However, to observe this effect, the propranolol needed to be administered one hour before the presentation of the story at consolidation and one hour before it’s reactivation at reconsolidation. While consolidation and reconsolidation studies in animals and humans have yielded conflicting results, this may depend on the type of stimuli used. The objective of the second paper of this thesis was to determine what type of information is most likely to be affected by propranolol during acquisition (consolidation) and reactivation (reconsolidation). To do this, the elements of the emotional story were divided according their emotionality (emotional vs. neutral) and centrality (central vs. peripheral). The results demonstrated that propranolol blocks the consolidation of all central information, but it affects selectively the central-emotional story elements at reconsolidation. Our group previously demonstrated that treatment with propranolol is able to reduce the symptoms of PTSD in a clinical population. In this thesis, we investigated whether it could also reduce the implicit memory of a traumatic event. Propranolol was administered on 6 different occasions (once a week over a period of 6 weeks) to participants upon reactivation of their traumatic event. The results unveiled that treatment with propranolol was able to decrease the participants’ psychophysiological responses to their traumatic script at one week post-treatment and at the 4 months follow-up. In sum, this thesis reports results suggesting that propranolol is able to block the consolidation and reconsolidation of emotional memories in humans when it is administered one hour before acquisition or before reactivation. Furthermore, this thesis suggests that propranolol impairs selectively central-emotional type of information and that it has the ability to dampen declarative emotional memory in healthy subjects, but also implicit memory in subjects suffering from PTSD. Hence, these results open the way to create new treatments for psychopathologies having at their core an intense emotional memory

Keyphrases: Reconsolidation, Propranolol, Consolidation, Reactivation, Memory, Posttraumatic stress disorder, Emotion