title: Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress.
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.
authors.affiliation: Department of Psychology, Texas A&M University, College Station, TX 77843;
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fitzgerald
authors.affiliation: Department of Psychology, Texas A&M University, College Station, TX 77843; Institute for Neuroscience, Texas A&M University, College Station, TX 77843.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Giustino
authors.affiliation: Department of Psychology, Texas A&M University, College Station, TX 77843; Institute for Neuroscience, Texas A&M University, College Station, TX 77843.
authors.forename: Jocelyn R
authors.initials: JR
authors.lastname: Seemann
authors.affiliation: Department of Psychology, Texas A&M University, College Station, TX 77843; Institute for Neuroscience, Texas A&M University, College Station, TX 77843 maren@tamu.edu.
authors.forename: Stephen
authors.identifier: http://orcid.org/0000-0002-9342-7411
authors.initials: S
authors.lastname: Maren
mesh_terms: D000200:Action Potentials; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000502:physiology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D013315:Stress, Psychological
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D009638:Norepinephrine
keywords: extinction; fear; prefrontal cortex; propranolol; rat