estradiol-3-benzoate and Depression--Postpartum

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 ERbeta 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 After Day 23, "postpartum" rats were withdrawn from the hormone regimen (mimicking the postpartum decrease in gonadal hormones), and then received daily injections of compounds indicated (DPN, EB, IMI).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.

Topics: Analysis of Variance; Animals; Antidepressive Agents; Body Weight; Depression, Postpartum; Disease Models, Animal; Drug Administration Routes; Drug Administration Schedule; Estradiol; Female; Food Preferences; Imipramine; Nitriles; Ovariectomy; Postpartum Period; Pregnancy; Propionates; Rats; Rats, Long-Evans; Substance Withdrawal Syndrome; Sucrose; Sweetening Agents; Time Factors

Approximately 15% of child-bearing women develop postpartum depression (PPD), and many women with PPD experience anxious symptoms. It has been proposed that PPD is precipitated by the dramatic decline in reproductive hormones that occurs just after childbirth. To examine this hypothesis, ovariectomized female Sprague-Dawley rats underwent a hormone-simulated pregnancy (HSP) regimen; during the subsequent hormone withdrawal period, rats were tested in the forced swim test or elevated plus-maze, animal models of depression and anxiety, respectively. The HSP regimen consisted of injections with progesterone and escalating doses of estradiol benzoate for 22 days; control rats received daily vehicle injections. One, two, four or seven days after the last hormone injection, separate groups of rats were tested once on either the forced swim test or the elevated plus-maze. To examine any hormone withdrawal-induced changes in activity levels, spontaneous locomotor activity was measured at the same time points. At 2 and 4 days after the last hormone injection, HSP-treated females displayed significant increases in immobility relative to vehicle-treated females in the forced swim test. Behavior on the elevated plus-maze did not differ between the HSP and control groups at any of the withdrawal time points. There were also no differences in spontaneous locomotor activity between the HSP and control females at any of the withdrawal time points. The results of this study suggest that postpartum hormone withdrawal may contribute to depressive symptoms experienced after giving birth, and that the HSP-hormone withdrawal protocol may provide a useful animal model of PPD.

Topics: Animals; Behavior, Animal; Depression, Postpartum; Disease Models, Animal; Estradiol; Female; Maternal Behavior; Maze Learning; Motor Activity; Naphthalenes; Ovariectomy; Oxepins; Progesterone; Rats; Rats, Sprague-Dawley; Substance Withdrawal Syndrome; Swimming; Time Factors