title: Estrogen disrupts the inhibition of fear in female rats, possibly through the antagonistic effects of estrogen receptor alpha (ERalpha) and ERbeta.
abstract: The ambiguous role of estrogen in emotional learning may result from opposing actions of estrogen receptor alpha (ERalpha) and ERbeta. Using a fear-conditioning paradigm called the AX+, BX- discrimination, in which cue A comes to elicit fear and cue B becomes a safety signal, we examined the effect of 17beta-estradiol (E) and selective ERalpha and ERbeta agonists on excitatory and inhibitory fear learning. Gonadectomized (GDX) male and female rats implanted with E or selective ERalpha or ERbeta agonists were trained on the AX+, BX- discrimination and tested periodically to A, B, and AB. GDX sham-implanted male and female rats and GDX E-implanted males, but not GDX E-implanted females, exhibited less fear to AB than to A, suggesting that estrogen interferes with generalization of safety signals in female rats. ERalpha and ERbeta agonists disrupted discrimination learning in both sexes. ERalpha-implanted groups had higher fear responses to all cues than did ERbeta-implanted groups, suggesting that these two receptors have opposing effects in aversive discrimination learning. In contrast, neither E nor ERalpha and ERbeta agonists affected single-cue fear conditioning in either sex. These data suggest that E does not enhance fear in emotional learning but acts to disrupt the inhibition of fear in females only.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, and The Center for Behavioral Neuroscience, Atlanta, Georgia 30329, USA. dtoufex@emory.edu
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Toufexis
authors.forename: Karyn M
authors.initials: KM
authors.lastname: Myers
authors.forename: Michael E
authors.initials: ME
authors.lastname: Bowser
authors.forename: Michael
authors.initials: M
authors.lastname: Davis
mesh_terms: D000818:Animals; D002369:Castration; D003213:Conditioning, Psychological / Q000187:drug effects; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004343:Drug Implants; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000187:drug effects / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D012727:Sex Characteristics