Disorders of anxiety and fear dysregulation are highly prevalent. It is known that these disorders affect women approximately two times more than they affect men, and this disparity is thought to be related to hormone regulation, yet the underlying mechanism of hormone regulation of the fear circuit in either sex remains unknown. The purpose of this Exploratory/ Developmental Grant proposal, in response to PA-03-169, is to develop a more informative and accurate method to determine the effect that gonadal hormones have on fear in both male and female animals. Here, we will employ a new adapted version of the discrimination training paradigm AX+.BX-, along with the use of highly specific estrogen receptor agonists and an androgen receptor-specific testosterone metabolite, to measure the effect that activation of specific gonadal steroid receptors have on both the activation and inhibition of fear.
The specific aims of this project are: 1. to validate the use of the AX+, BX- discrimination learning paradigm as a model for examining hormone modulation of fear acquisition, expression and inhibition. 2. to use this model to examine: the effect of gonadal steroids on fear acquisition, and the effect of gonadal steroids on fear expression, in gonadectomized male and female rats. Data from these studies will begin to elucidate the specific effects that these steroid hormones have on very particular aspects of emotional memory formation and expression in general, and moreover, these studies will help to clarify the contribution that the various gonadal steroids make to fear learning in each individual sex . Results from these investigations would not only speak to the development, and expression of emotional learning within each individual sex, but will also begin to address the gender disparity in the occurrence of PTSD, depression and anxiety illness, and panic disorder. ? ? ?
| Jovanovic, Tanja; Norrholm, Seth D; Blanding, Nineequa Q et al. (2010) Fear potentiation is associated with hypothalamic-pituitary-adrenal axis function in PTSD. Psychoneuroendocrinology 35:846-57 |
| Shepard, Kathryn N; Michopoulos, Vasiliki; Toufexis, Donna J et al. (2009) Genetic, epigenetic and environmental impact on sex differences in social behavior. Physiol Behav 97:157-70 |
| Toufexis, Donna J; Myers, Karyn M; Bowser, Michael E et al. (2007) Estrogen disrupts the inhibition of fear in female rats, possibly through the antagonistic effects of estrogen receptor alpha (ERalpha) and ERbeta. J Neurosci 27:9729-35 |
