Genetic strain differences in learned fear inhibition associated with variation in neuroendocrine, autonomic, and amygdala dendritic phenotypes.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
M CampAndrew Holmes

Abstract

Mood and anxiety disorders develop in some but not all individuals following exposure to stress and psychological trauma. However, the factors underlying individual differences in risk and resilience for these disorders, including genetic variation, remain to be determined. Isogenic inbred mouse strains provide a valuable approach to elucidating these factors. Here, we performed a comprehensive examination of the extinction-impaired 129S1/SvImJ (S1) inbred mouse strain for multiple behavioral, autonomic, neuroendocrine, and corticolimbic neuronal morphology phenotypes. We found that S1 exhibited fear overgeneralization to ambiguous contexts and cues, impaired context extinction and impaired safety learning, relative to the (good-extinguishing) C57BL/6J (B6) strain. Fear overgeneralization and impaired extinction was rescued by treatment with the front-line anxiety medication fluoxetine. Telemetric measurement of electrocardiogram signals demonstrated autonomic disturbances in S1 including poor recovery of fear-induced suppression of heart rate variability. S1 with a history of chronic restraint stress displayed an attenuated corticosterone (CORT) response to a novel, swim stressor. Conversely, previously stress-naive S1 showed ...Continue Reading

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Citations

Dec 12, 2013·Trends in Pharmacological Sciences·Ozge Gunduz-CinarAndrew Holmes
Mar 21, 2012·Proceedings of the National Academy of Sciences of the United States of America·Catherine A HartleyCharles E Glatt
Jul 9, 2013·Biology of Mood & Anxiety Disorders·Kathryn MacphersonAndrew Holmes
Nov 16, 2013·Neurobiology of Learning and Memory·Paul J FitzgeraldAndrew Holmes
Mar 13, 2014·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Andrea Hetzel, J Amiel Rosenkranz
Sep 26, 2013·Proceedings of the National Academy of Sciences of the United States of America·Kiriana K CowansageJoseph E Ledoux
Dec 25, 2012·Trends in Neurosciences·Andrew Holmes, Nicolas Singewald
Dec 9, 2015·Neurobiology of Learning and Memory·Vitor Castro-GomesLuke R Johnson
Jul 29, 2015·Trends in Neurosciences·África FloresFernando Berrendero
Oct 31, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Ozge Gunduz-CinarAndrew Holmes
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Jan 1, 2012·Scientifica·Judith R Homberg
Jun 25, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Stephen Maren, Andrew Holmes
Dec 17, 2014·Molecular Psychiatry·P J FitzgeraldA Holmes
May 20, 2014·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Dina PopovaNina N Karpova
Aug 21, 2013·Proceedings of the National Academy of Sciences of the United States of America·Lauren DePoyAndrew Holmes
Sep 6, 2014·Frontiers in Behavioral Neuroscience·Stephanie J TemmeGeoffrey G Murphy
Sep 13, 2016·PLoS Computational Biology·Yuzhe LiHonda Naoki
Nov 7, 2016·Alcohol·Lindsay R HalladayAndrew Holmes
Oct 25, 2016·PloS One·Thomas F GiustinoStephen Maren
Apr 1, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jennifer C ChanTracy L Bale
Dec 26, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Pere Boadas-VaelloJordi Llorens
Oct 14, 2017·Genes, Brain, and Behavior·C P Murphy, N Singewald
Jun 17, 2014·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·África FloresFernando Berrendero
Nov 1, 2018·Psychopharmacology·Nicolas Singewald, Andrew Holmes
Feb 12, 2019·Behavioural Pharmacology·Dario Aspesi, Graziano Pinna
Jan 10, 2018·Molecular Psychiatry·Ozge Gunduz-CinarAndrew Holmes
Apr 12, 2019·Genes, Brain, and Behavior·Victor A CazaresGeoffrey G Murphy
Jan 30, 2020·Current Protocols in Neuroscience·Hadley C Bergstrom
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May 15, 2020·Molecular Psychiatry·Shannon J MooreVictor A Cazares

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