Estrous cycle phase and gonadal hormones influence conditioned fear extinction

Abstract Gonadal hormones modulate fear acquisition, but less is known about the influence of gonadal hormones on fear extinction. We assessed sex differences and the influence of gonadal hormone fluctuations and exogenous manipulations of estrogen and progesterone on acquisition, extinction learnin...

Full description

Saved in:

Bibliographic Details
Published in:	Neuroscience Vol. 164; no. 3; pp. 887 - 895
Main Authors:	Milad, M.R, Igoe, S.A, Lebron-Milad, K, Novales, J.E
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Ltd 15-12-2009 Elsevier
Subjects:	Animals anxiety Anxiety Disorders - etiology Anxiety Disorders - metabolism Anxiety Disorders - physiopathology Biological and medical sciences Brain - physiology conditioned fear Conditioning (Psychology) - drug effects Conditioning (Psychology) - physiology estrogen Estrogens - metabolism Estrogens - pharmacology estrous cycle Estrous Cycle - drug effects Estrous Cycle - physiology Extinction, Psychological - drug effects Extinction, Psychological - physiology Fear - drug effects Fear - physiology Female Freezing Reaction, Cataleptic - drug effects Freezing Reaction, Cataleptic - physiology Fundamental and applied biological sciences. Psychology Gonadal Steroid Hormones - metabolism Gonadal Steroid Hormones - secretion Learning - drug effects Learning - physiology Male Metestrus - drug effects Metestrus - physiology Neurology Neuropsychological Tests Photic Stimulation Proestrus - drug effects Proestrus - physiology progesterone Progesterone - metabolism Progesterone - pharmacology Rats Rats, Sprague-Dawley Receptors, Estrogen - drug effects Receptors, Estrogen - metabolism Sex Characteristics Testosterone - metabolism Vertebrates: nervous system and sense organs Ext estrogen post-traumatic stress disorder E fulvestrant progesterone vmPFC LTP mifepristone Pro P Vehicle SE extinction analysis of variance ANOVA metestrus Fulv proestrus light-emitting diode estradiol Cond estrogen receptor conditioned fear LED Mif ER PTSD anxiety conditioning ventromedial prefrontal cortex Veh estrous cycle standard error of the mean Met long-term potentiation Fear Estrogen Anxiety Estrous cycle Progesterone Sex steroid hormone Ovarian hormone
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Abstract Gonadal hormones modulate fear acquisition, but less is known about the influence of gonadal hormones on fear extinction. We assessed sex differences and the influence of gonadal hormone fluctuations and exogenous manipulations of estrogen and progesterone on acquisition, extinction learning and extinction recall in a 3 day auditory fear conditioning and extinction protocol. Experiments were conducted on males and naturally cycling female rats. Regarding female rats, significant differences in fear extinction were observed between subgroups of females, depending on their phase of the estrous cycle. Extinction that took place during the proestrus (high estrogen/progesterone) phase was more fully consolidated, as evidenced by low freezing during a recall test. This suggests that estrogen and/or progesterone facilitate extinction. In support of this, injection of both estrogen and progesterone prior to extinction learning in female rats during the metestrus phase of the cycle (low estrogen/progesterone) facilitated extinction consolidation, and blockade of estrogen and progesterone receptors during the proestrus phase impaired extinction consolidation. When comparing male to female rats without consideration of the estrous cycle phase, no significant sex differences were observed. When accounting for cycle phase in females, sex differences were observed only during extinction recall. Female rats that underwent extinction during the metestrus phase showed significantly higher freezing during the recall test relative to males. Collectively, these data suggest that gonadal hormones influence extinction behavior possibly by influencing the function of brain regions involved in the consolidation of fear extinction. Moreover, the elevated fear observed in female relative to male rats during extinction recall suggests that gonadal hormones may in part play a role in the higher prevalence of anxiety disorders in women.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0306-4522 1873-7544
DOI:	10.1016/j.neuroscience.2009.09.011