title: Early post-stressor intervention with propranolol is ineffective in preventing posttraumatic stress responses in an animal model for PTSD.
abstract: The therapeutic value of β-adrenoceptor blockage, using propranolol, in the aftermath of traumatic experience is uncertain. A prospective, controlled animal model of posttraumatic stress disorder (PTSD) was employed to assess the effects of propranolol on long-term behavioral responses to stress. Animals exposed to predator scent stress received a single bolus of propranolol (10 or 15mg/kg) or vehicle 1h post-exposure. Outcomes were assessed using the elevated plus-maze (EPM) and acoustic startle response (ASR) at 30days and freezing response to a trauma reminder (unsoiled litter) on Day 31. Individual animals were classified as having "extreme", "partial" and "minimal" behavioral responses, according to pre-set cut-off criteria for EPM and ASR response patterns. The physiological efficacy of the doses of propranolol was verified by collecting cardiovascular data telemetrically (from exposed or unexposed individuals given propranolol or vehicle). The effect of propranolol on long-term memory was verified using a non-spatial memory task. Both doses of propranolol effectively reduced mean heart rate and impaired the object-recognition task, as expected. No significant effect on prevalence rates of PTSD-like behavioral responses or on trauma reminder response was observed for either dose of propranolol as compared to vehicle. Despite adequate efficacy in terms of heart rate and disruption of memory, single-dose, post-stress β-blockage with propranolol was ineffective in reducing onset of PTSD-like behavioral disruption and trauma cue responses in the long term. Traumatic stress-related processes appear to be affected differently than the others.
authors.affiliation: Ministry of Health Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. hagitc@bgu.ac.il
authors.forename: Hagit
authors.initials: H
authors.lastname: Cohen
authors.forename: Zeev
authors.initials: Z
authors.lastname: Kaplan
authors.forename: Ori
authors.initials: O
authors.lastname: Koresh
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matar
authors.forename: Amir B
authors.initials: AB
authors.lastname: Geva
authors.forename: Joseph
authors.initials: J
authors.lastname: Zohar
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D003463:Cues; D004195:Disease Models, Animal; D006339:Heart Rate; D007279:Injections, Subcutaneous; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D057567:Memory, Long-Term / Q000187:drug effects; D009248:Nadolol / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D013315:Stress, Psychological / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D009248:Nadolol; D011433:Propranolol