Effects of the Estrous Cycle on Neuronal Activation in the Bed Nucleus of the Stria Terminalis of Fear-Conditioned Female Rats

Abstract

Women are much more likely than men to develop trauma- and anxiety-related disorders over their lifetime. One possible contributing factor is that unlike men, women experience large fluctuations in ovarian steroid hormones, like progesterone. Previous studies have suggested that high levels of progesterone reduce the expression of fear in female rats. The effect may be derived from allopregnanolone (ALLO), a metabolite of progesterone. ALLO, a positive allosteric modulator of ɣ-aminobutyric acid type A (GABAA) receptors, may influence activity in the bed nucleus of the stria terminalis (BNST), a brain area that is important for the expression of conditioned fear. GABA is the major inhibitory neurotransmitter in the brain and contributes to the suppression of anxiety responses. The proposed study seeks to determine the effect of fluctuating progesterone levels on BNST cell activation during the expression of conditioned fear in female rats. We hypothesize that rats tested when progesterone levels are high will have lower BNST cell activation compared to rats tested when progesterone levels are low. To this end, animals will be trained and tested at estrous cycle stages with either high or low levels of progesterone under the Pavlovian fear conditioning paradigm. Progesterone levels will be measured using blood samples. BNST cell activation will be measured by quantifying the number of c-fos-expressing cells within this brain region. By exploring how progesterone influences BNST cell activation during conditioned fear, a greater understanding of the susceptibility of women to trauma and stress disorders, such as posttraumatic stress disorder (PTSD), may be achieved.