Noradrenergic regulation of fear and drug-associated memory reconsolidation

Neuropsychopharmacology. 2015 Mar;40(4):793-803. doi: 10.1038/npp.2014.243. Epub 2014 Sep 12.

Abstract

Emotional and traumatic experiences lead to the development of particularly strong memories that can drive neuropsychiatric disorders, such as posttraumatic stress disorder (PTSD) and drug addiction. Disruption of these memories would therefore serve as a powerful treatment option, and targeting the pathologic emotional, but not declarative, component of a memory would be ideal for clinical intervention. Research reveals that after retrieval of a consolidated memory, the memory can be destabilized, and must then be reconsolidated through synaptic plasticity to allow subsequent retrieval. Disruption of reconsolidation-related plasticity would therefore impair specific, reactivated memories. Noradrenergic signaling strengthens synaptic plasticity and is essential for encoding the emotional components of memory. Consistent with this, investigations have now revealed that noradrenergic signaling is a critical mechanism for reconsolidation of emotional memories in rodent and human models. Here, we discuss these investigations and promising clinical trials indicating that disruption of noradrenergic signaling during reconsolidation may abolish the pathologic emotional, but not declarative, component of memories allowing alleviation of neuropsychiatric disorders including PTSD and drug addiction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Fear / drug effects
  • Fear / physiology*
  • Humans
  • Memory / drug effects
  • Memory / physiology*
  • Norepinephrine / metabolism*
  • Norepinephrine / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • Norepinephrine