The impact of motherhood on the extinction of learned fear

Abstract

This thesis investigated the impact of female reproductive experience on fear regulation. The first three experimental chapters examined fear extinction, the laboratory basis of exposure therapy for anxiety disorders, in female rats. In the first Experimental series (Chapter 2), I found that fear extinction was NMDAR-dependent in nulliparous (virgin), but not primiparous (reproductively experienced) rats. Contrastingly, fear conditioning appeared to be NMDAR-dependent in both nulliparous and primiparous rats. It also emerged that primiparous rats exhibited higher levels of freezing during extinction training, extinction recall, and conditioning recall compared to nulliparous rats. The next Experimental series (Chapter 3) investigated the effect of d-cycloserine and estradiol on fear extinction in nulliparous and primiparous rats. Both drugs were effective in enhancing extinction recall among nulliparous rats, but not primiparous rats. In Chapter 3, I also found that the expression of genes coding for the NMDAR subunits, NR2A and NR2B, and the classical estrogen receptors, ERα and ERβ, may be upregulated in the hippocampus following reproductive experience. In Chapter 4, I used a hierarchical multiple regression analysis to identify and compare hormonal and behavioural predictors of fear extinction between nulliparous and primiparous rats. This analysis revealed both overlapping (e.g., extinction rate and late extinction) and dissociable (e.g., estrous phase) predictors of fear extinction between these groups of rats. Moreover, follow-up analyses demonstrated that primiparous rats exhibited extinction recall levels that were between that of nulliparous rats extinguished during metestrus and nulliparous rats extinguished during proestrus. Finally, in Chapter 5, I sought to translate the findings of my animal studies to clinical settings by examining how treatment outcomes compare between men and women of varying reproductive status receiving internet-based cognitive behavioural therapy (iCBT), a core component of which is exposure therapy. I found that these groups largely showed equal benefit from iCBT. Together, these findings suggest that reproductive experience may alter the hormonal, neurobiological and behavioural features of fear extinction in female rats, but may not alter the efficacy of psychological treatments that are modelled upon fear extinction among women. The theoretical and clinical implications of these findings are discussed.