Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress

Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):E3729-37. doi: 10.1073/pnas.1500682112. Epub 2015 Jun 29.

Abstract

Stress-induced impairments in extinction learning are believed to sustain posttraumatic stress disorder (PTSD). Noradrenergic signaling may contribute to extinction impairments by modulating medial prefrontal cortex (mPFC) circuits involved in fear regulation. Here we demonstrate that aversive fear conditioning rapidly and persistently alters spontaneous single-unit activity in the prelimbic and infralimbic subdivisions of the mPFC in behaving rats. These conditioning-induced changes in mPFC firing were mitigated by systemic administration of propranolol (10 mg/kg, i.p.), a β-noradrenergic receptor antagonist. Moreover, propranolol administration dampened the stress-induced impairment in extinction observed when extinction training is delivered shortly after fear conditioning. These findings suggest that β-adrenoceptors mediate stress-induced changes in mPFC spike firing that contribute to extinction impairments. Propranolol may be a helpful adjunct to behavioral therapy for PTSD, particularly in patients who have recently experienced trauma.

Keywords: extinction; fear; prefrontal cortex; propranolol; rat.

Publication types

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

MeSH terms

  • Action Potentials
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Extinction, Psychological / drug effects*
  • Fear / physiology*
  • Norepinephrine / antagonists & inhibitors*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiopathology*
  • Propranolol / pharmacology
  • Rats
  • Stress, Psychological*

Substances

  • Adrenergic beta-Antagonists
  • Propranolol
  • Norepinephrine