Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala.
Consolidation is a process through which labile memories are made persistent [Science 287 (2000) 248]; [Annu Rev Psychol 55 (2004) 51]. When retrieved, a consolidated memory is rendered labile again and undergoes reconsolidation [Learn Mem 7 (2000) 73]; [Trends Neurosci 26 (2003) 65]). Reconsolidation thus offers the opportunity to manipulate memory after it is formed, and may therefore provide a means of treating intrusive memories associated with post-traumatic stress disorder (PTSD). Reconsolidation is most usually studied using protein synthesis inhibitors, which is not practical in humans. However, the beta adrenergic receptor antagonist propranolol impairs consolidation of declarative memory in humans [Science 287 (2000) 248]; [Nature 371 (1994) 702] and consolidation and reconsolidation of inhibitory avoidance learning in rats [Brain Res 368 (1986) 125]; [J Neurosci 19 (1999) 6623]. Here, we show that systemic or intra-amygdala infused propranolol blocks reconsolidation but not consolidation. If the effects on reconsolidation are verified in humans, the results would suggest the possibility that propranolol after memory retrieval might be an effective way of treatment of intrusive memories in PTSD. That the systemic effects of propranolol on reconsolidation are achieved via an action in the amygdala is especially important in light of the fact that PTSD involves alterations in the amygdala [Arch Gen Psychiatry 53 (1996) 380].
Debiec
J
J
W. M. Keck Foundation, Laboratory of Neurobiology, Center for Neural Science, New York University, 4 Washington Place, Room 809, New York, NY 10003, USA. jacek@cns.nyu.edu
Ledoux
J E
JE
D000161:Acoustic Stimulation; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000679:Amygdala / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D003463:Cues; D005239:Fear / Q000523:psychology*; D007267:Injections; D007274:Injections, Intraperitoneal; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D009638:Norepinephrine