Role of estradiol withdrawal in ‘anhedonic’ sucrose consumption: A model of postpartum depression

Previously, a hormone-simulated pregnancy (HSP), and the subsequent ‘postpartum’ withdrawal in estradiol has been shown to precipitate depressive-like behaviours in the forced swim test in female rats. In this study, we used the HSP and ‘postpartum’ withdrawal to investigate the impact on sucrose consumption, a model of anhedonia. Rats were assigned to “postpartum”, “postpartum” + EB (estradiol benzoate), “postpartum” + IMI (imipramine; a tricyclic antidepressant), “postpartum” + DPN (diarylpropionitrile; an ERβ agonist), or ovariectomized (OVX) controls and OVX + IMI treatments. All “postpartum” 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 After Day 23, “postpartum” rats were withdrawn from the hormone regimen (mimicking the postpartum decrease in gonadal hormones), and then received daily injections of compounds indicated (DPN, EB, IMI). Rats were tested for consumption of, and preference for, sucrose weekly at baseline, during ‘pregnancy’ and on ‘Postpartum’ Days 2–3. During the ‘postpartum’ period rats in the “postpartum” group had lower sucrose consumption and preference compared to during late-‘pregnancy’, but no decrease in ‘postpartum’ consumption or preference was seen in any other groups except “postpartum” + IMI and a decrease in sucrose preference only in the postpartum + EB group from mid-‘pregnancy’ to ‘postpartum’. The OVX  + IMI group had decreased sucrose consumption relative to OVX controls, suggesting a negative effect of imipramine on sucrose consumption. Together, these results suggest an important, though complex, role for gonadal hormones in the behavioral changes accompanying this model of depression.