Stressor controllability and learned helplessness: the roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor

Neurosci Biobehav Rev. 2005;29(4-5):829-41. doi: 10.1016/j.neubiorev.2005.03.021.


The term 'learned helplessness' refers to a constellation of behavioral changes that follow exposure to stressors that are not controllable by means of behavioral responses, but that fail to occur if the stressor is controllable. This paper discusses the nature of learned helplessness, as well as the role of the dorsal raphe nucleus, serotonin, and corticotropin-releasing hormone in mediating the behavioral effects of uncontrollable stressors. Recent research indicates that (a) uncontrollable stressors sensitize serotonergic neurons in the dorsal raphe, and that a corticotropin-releasing factor-related ligand, acting at the Type II receptor, is essential to this sensitization process, and (b) the consequent exaggerated release of serotonin in response to subsequent input is at least in part responsible for the behavioral changes that occur. Finally, implications for the general role of corticotropin-releasing hormone in stress-related phenomena and for the learned helplessness paradigm as an animal model of either depression or anxiety are discussed.

Publication types

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

MeSH terms

  • Animals
  • Anxiety / metabolism
  • Anxiety / physiopathology
  • Behavior, Animal
  • Corticotropin-Releasing Hormone / metabolism*
  • Helplessness, Learned*
  • Humans
  • Raphe Nuclei / metabolism
  • Raphe Nuclei / physiopathology*
  • Serotonin / metabolism*
  • Stress, Physiological / metabolism
  • Stress, Physiological / physiopathology*


  • Serotonin
  • Corticotropin-Releasing Hormone