Investigating an animal model of postpartum depression : the role of estradiol withdrawal in changes to adult hippocamp

'Estradiol withdrawal' after pregnancy is hypothesized to precipitate depressive symptoms in vulnerable women. In this study, a hormonally-simulated 'pregnancy' was induced in ovariectomized female rats and the effect of a 'postpartum' drop in estradiol was examined on hippocampal cell proliferation (Experiment 1) and sucrose consumption, a model of anhedonia (Experiment 2). All non-sham groups were ovariectomized prior to treatment. Rats were randomly assigned to "pregnant", "pregnant + EB (estradiol benzoate)", "pregnant + IMI (imipramine; a tricyclic antidepressant)", "pregnant + DPN (diarylpropionitrile; an ERβ agonist)", "sham" or "ovariectomized (OVX)" controls and "sham/ovx + IMI" treatments. All "pregnant" groups received daily hormone injections (estradiol and progesterone) over 23 days to simulate pregnancy, while IMI groups also received daily injections of imipramine. After Day 23 of the "hormone simulated pregnancy", "pregnant" rats were withdrawn from the hormone regime (mimicking the postpartum drop in gonadal hormones), while other "pregnancy" groups received daily injections of compounds indicated (DPN, EB, IMI). In Experiment 1, on 'Postpartum' Day 3, all rats were injected with bromodeoxyuridine and perfused 24 hours later to assess cell proliferation and cell death, in the dentate gyrus. In Experiment 2 groups of rats were tested for consumption of, and preference for, sucrose weekly throughout 'pregnancy' and on 'Postpartum' Days 2-4. The "pregnant" group had significantly less cell proliferation in the dentate gyrus compared to all other groups except "pregnant +EB". Estradiol withdrawal after 'pregnancy' decreased cell proliferation and this decrease was reversed/prevented by imipramine or DPN treatment. Chronic imipramine increased cell proliferation in sham, but not ovariectomized, rats, suggesting that the imipramine-induced increase in hippocampal cell proliferation is related to reproductive status. In Experiment 2, all groups except "OVX" showed a significant decrease in body weight. Furthermore, there were trends for "pregnant" and "pregnant + EB" groups to have lower sucrose consumption and preference in the postpartum period compared to pregnancy. "OVX + IMI" had decreased sucrose consumption relative to OVX controls, suggesting a negative effect of imipramine on consumption. Together, these results suggest an important, though complex, role for gonadal hormones in the behavioural and cellular changes accompanying this depression model.Medicine, Faculty ofGraduat