title: Chronic corticosterone exposure persistently elevates the expression of memory-related genes in the lateral amygdala and enhances the consolidation of a Pavlovian fear memory.
abstract: Chronic exposure to stress has been widely implicated in the development of anxiety disorders, yet relatively little is known about the long-term effects of chronic stress on amygdala-dependent memory formation. Here, we examined the effects of a history of chronic exposure to the stress-associated adrenal steroid corticosterone (CORT) on the consolidation of a fear memory and the expression of memory-related immediate early genes (IEGs) in the lateral nucleus of the amygdala (LA). Rats received chronic exposure to CORT (50 μg/ml) in their drinking water for 2 weeks and were then titrated off the CORT for an additional 6 days followed by a 2 week 'wash-out' period consisting of access to plain water. Rats were then either sacrificed to examine the expression of memory-related IEG expression in the LA or given auditory Pavlovian fear conditioning. We show that chronic exposure to CORT leads to a persistent elevation in the expression of the IEGs Arc/Arg3.1 and Egr-1 in the LA. Further, we show that rats with a history of chronic CORT exposure exhibit enhanced consolidation of a fear memory; short-term memory (STM) is not affected, while long-term memory (LTM) is significantly enhanced. Treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine following the chronic CORT exposure period was observed to effectively reverse both the persistent CORT-related increases in memory-related IEG expression in the LA and the CORT-related enhancement in fear memory consolidation. Our findings suggest that chronic exposure to CORT can regulate memory-related IEG expression and fear memory consolidation processes in the LA in a long-lasting manner and that treatment with fluoxetine can reverse these effects.
authors.affiliation: Department of Psychology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Monsey
authors.affiliation: Department of Psychology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Lara M
authors.initials: LM
authors.lastname: Boyle
authors.affiliation: Department of Psychology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Melinda L
authors.initials: ML
authors.lastname: Zhang
authors.affiliation: Department of Psychology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Caroline P
authors.initials: CP
authors.lastname: Nguyen
authors.affiliation: Department of Psychology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Hope G
authors.initials: HG
authors.lastname: Kronman
authors.affiliation: Department of Psychiatry, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Kristie T
authors.initials: KT
authors.lastname: Ota
authors.affiliation: Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut, United States of America; Department of Psychiatry, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Duman
authors.affiliation: Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut, United States of America; Department of Psychiatry, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Jane R
authors.initials: JR
authors.lastname: Taylor
authors.affiliation: Department of Psychology, The City University of New York, New York, New York, United States of America; Center for Study of Gene Structure and Function, Hunter College, The City University of New York, New York, New York, United States of America; The Graduate Center, The City University of New York, New York, New York, United States of America.
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Schafe
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000008:administration & dosage*; D005239:Fear / Q000523:psychology*; D005473:Fluoxetine / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early; D008297:Male; D008568:Memory; D051381:Rats; D015398:Signal Transduction; D013315:Stress, Psychological; D013569:Synapses / Q000378:metabolism
chemical_list: D005473:Fluoxetine; D003345:Corticosterone