Pharmacological facilitation of fear extinction and the search for adjunct treatments for anxiety disorders--the case of yohimbine

Trends Pharmacol Sci. 2010 Jan;31(1):2-7. doi: 10.1016/ Epub 2009 Dec 28.


There is current interest in identifying drugs that facilitate fear extinction, as this form of learning is the basis of certain cognitive therapies for anxiety disorders. Following an initial report several years ago that the alpha2-adrenoreceptor antagonist yohimbine facilitated extinction in mice, more recent studies have shown mixed effects or even impairment. It has become clear that the effect of yohimbine on extinction depends on a number of factors, including genetic background, contextual variables and the presence of competing behaviors. To what extent theses effects of yohimbine are mediated through the alpha2-adrenoreceptor, as opposed to other sites of action, is also uncertain. More work is needed before this drug can be approved as a pharmacological adjunct for extinction-based therapies. More generally, the case of yohimbine may serve as a model for the development of other extinction facilitators.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / physiopathology
  • Behavior, Animal / drug effects
  • Extinction, Psychological / drug effects
  • Fear / drug effects
  • Humans
  • Mice
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Yohimbine / pharmacology*


  • Adrenergic alpha-Antagonists
  • Receptors, Adrenergic, alpha-2
  • Yohimbine