Hippocampal β-adrenergic system modulates recognition memory reconsolidation

Abstract Targeting reconsolidation with propranolol, a blocker of β-adrenergic receptors (β-ARs), emerged as a potential treatment for maladaptive memories such as those involved in posttraumatic stress disorder (PTSD). Reconsolidation targeting treatments for PTSD are becoming a common practice in the clinic and it is important to unveil any side effects upon ‘non-targeted’ memories. While previous studies have focused on propranolol’s effects on the reconsolidation of emotional/distressful memories, the present study asked whether propranolol is involved in the reconsolidation of recognition memories - by assessing its effects on distinct memory components and the role of the hippocampus. Rats performed an object recognition (OR) task where they were exposed to different objects: A and B presented during the sample phase; A and C presented during the reactivation phase; and D in combination of either A, B, or C during a final test. Intra-hippocampal injections of propranolol (5 µg or 10 µg) were conducted immediately after the reactivation session. Propranolol infusions consistently impaired the addition of novel information to the previously consolidated memory trace regardless of dose, and the retention of familiar objects was not affected. Higher doses of propranolol also hindered memory of a familiar object that was not presented during the reactivation session, but was previously placed at the same location where novel information was presented during reactivation. The present results shed light on the role of β-ARs on the reconsolidation of different memory components and argue for the need for further studies examining possible recognition memory deficits following propranolol treatment. Graphical abstract Post-traumatic stress disorder is a chronic mental health condition, which may develop following direct or indirect exposure to a traumatic event. The administration of propranolol to individuals affected by this disorder before the reactivation of the trauma-related memory may diminish the symptoms of this mental condition. Here, we show that such treatment may have effects on non-targeted memories, other than the fear/distressful memory. In a series of experiments in rodents, we show that intra-hippocampal infusion of propranolol immediately after recalling and updating a recognition memory trace hampers the reconsolidation of the initial recognition memory trace during recall. This may lead to difficulties in recalling recent events related to declarative memories. In a high dose, propranolol treatment may also affect the conjunctive component (association between multiple elements) of the memory trace – in addition to the effect on the elemental component. This may lead, for example, to difficulties in locating a parked car in a non-usual location after the post-stress traumatic stress disorder therapy with propranolol. Highlights We established the role of the hippocampal β-adrenergic system in the reconsolidation of recognition memories. Propranolol treatment may impair the updating of recognition memory traces. High doses of propranolol may disrupt both elemental and conjunctive components of memory. Clinical treatment with high doses of propranolol for post-traumatic stress disorder may unintentionally affect non-pathological components of memories.