Sofia Leal Santos1, Michelle Stackmann2, Andrea Muñoz Zamora3, Alessia Mastrodonato4, Allegra V De Landri5, Nick Vaughan6, Briana K Chen2, Marcos Lanio7, Christine A Denny8. 1. Department of Psychiatry, Columbia University Irving Medical Center, New York, New York; Division of Systems Neuroscience, Research Foundation for Mental Hygiene Inc/New York State Psychiatric Institute, New York, New York; Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Portugal. 2. Neurobiology and Behavior Graduate Program, Columbia University, New York, New York. 3. Division of Systems Neuroscience, Research Foundation for Mental Hygiene Inc/New York State Psychiatric Institute, New York, New York. 4. Department of Psychiatry, Columbia University Irving Medical Center, New York, New York; Division of Systems Neuroscience, Research Foundation for Mental Hygiene Inc/New York State Psychiatric Institute, New York, New York. 5. Division of Systems Neuroscience, Research Foundation for Mental Hygiene Inc/New York State Psychiatric Institute, New York, New York; Columbia College, Columbia University, New York, New York. 6. Columbia College, Columbia University, New York, New York. 7. Medical Scientist Training Program, Columbia University Irving Medical Center, New York, New York; Neurobiology and Behavior Graduate Program, Columbia University, New York, New York. 8. Department of Psychiatry, Columbia University Irving Medical Center, New York, New York; Division of Systems Neuroscience, Research Foundation for Mental Hygiene Inc/New York State Psychiatric Institute, New York, New York. Electronic address: cad2125@cumc.columbia.edu.
Abstract
BACKGROUND: Posttraumatic stress disorder can develop after a traumatic event and results in heightened, inappropriate fear and anxiety. Although approximately 8% of the U.S. population is affected by posttraumatic stress disorder, only two drugs have been approved by the Food and Drug Administration to treat it, both with limited efficacy. Propranolol, a nonselective β-adrenergic antagonist, has shown efficacy in decreasing exaggerated fear, and there has been renewed interest in using it to treat fear disorders. METHODS: Here, we sought to determine the mechanisms by which propranolol attenuates fear by utilizing an activity-dependent tagging system, ArcCreERT2 x eYFP mice. 129S6/SvEv mice were administered a 4-shock contextual fear conditioning paradigm followed by immediate or delayed context reexposures. Saline or propranolol was administered either before or after the first context reexposure. To quantify hippocampal, prefrontal, and amygdalar memory traces, ArcCreERT2 x eYFP mice were administered a delayed context reexposure with either a saline or propranolol injection before context reexposure. RESULTS: Propranolol decreased fear expression only when administered before a delayed context reexposure. Fear memory traces were affected in the dorsal dentate gyrus and basolateral amygdala after propranolol administration in the ArcCreERT2 x eYFP mice. Propranolol acutely altered functional connectivity between the hippocampal, cortical, and amygdalar regions. CONCLUSIONS: These data indicate that propranolol may decrease fear expression by altering network-correlated activity and by weakening the reactivation of the initial traumatic memory trace. This work contributes to the understanding of noradrenergic drugs as therapeutic aids for patients with posttraumatic stress disorder.
BACKGROUND: Posttraumatic stress disorder can develop after a traumatic event and results in heightened, inappropriate fear and anxiety. Although approximately 8% of the U.S. population is affected by posttraumatic stress disorder, only two drugs have been approved by the Food and Drug Administration to treat it, both with limited efficacy. Propranolol, a nonselective β-adrenergic antagonist, has shown efficacy in decreasing exaggerated fear, and there has been renewed interest in using it to treat fear disorders. METHODS: Here, we sought to determine the mechanisms by which propranolol attenuates fear by utilizing an activity-dependent tagging system, ArcCreERT2 x eYFP mice. 129S6/SvEv mice were administered a 4-shock contextual fear conditioning paradigm followed by immediate or delayed context reexposures. Saline or propranolol was administered either before or after the first context reexposure. To quantify hippocampal, prefrontal, and amygdalar memory traces, ArcCreERT2 x eYFP mice were administered a delayed context reexposure with either a saline or propranolol injection before context reexposure. RESULTS: Propranolol decreased fear expression only when administered before a delayed context reexposure. Fear memory traces were affected in the dorsal dentate gyrus and basolateral amygdala after propranolol administration in the ArcCreERT2 x eYFP mice. Propranolol acutely altered functional connectivity between the hippocampal, cortical, and amygdalar regions. CONCLUSIONS: These data indicate that propranolol may decrease fear expression by altering network-correlated activity and by weakening the reactivation of the initial traumatic memory trace. This work contributes to the understanding of noradrenergic drugs as therapeutic aids for patients with posttraumatic stress disorder.
Authors: Jennifer N Perusini; Stephanie A Cajigas; Omid Cohensedgh; Sean C Lim; Ina P Pavlova; Zoe R Donaldson; Christine A Denny Journal: Hippocampus Date: 2017-07-20 Impact factor: 3.899
Authors: Thomas F Giustino; Jocelyn R Seemann; Gillian M Acca; Travis D Goode; Paul J Fitzgerald; Stephen Maren Journal: Neuropsychopharmacology Date: 2017-05-02 Impact factor: 7.853
Authors: Fabrício H M Do-Monte; Grasielle C Kincheski; Eloisa Pavesi; Regina Sordi; Jamil Assreuy; Antônio P Carobrez Journal: Neurobiol Learn Mem Date: 2010-07-25 Impact factor: 2.877
Authors: Sofia Leal Santos; Briana K Chen; Guilherme R Pereira; Vananh Pham; Christine A Denny Journal: Front Behav Neurosci Date: 2022-07-07 Impact factor: 3.617