"Post-partum steroid withdrawal-induced depression"
Principal Investigator: R M Craft
Abstract: Up to 15% of child-bearing women develop postpartum depression (PPD) in the weeks following delivery. Similar to major depression, PPD puts women at increased risk for the development of other psychological disorders (e.g., anxiety disorders, substance abuse disorders). Although PPD has many sequelae in common with major depression, the fact that it occurs only in women, and appears to differ from major depression in both etiology and treatment outcomes, suggests that PPD involves distinct physiological mechanisms. The goal of the proposed research is to develop a model of PPD in the female rat which would ultimately provide information about what causes PPD (how brain function changes during the postpartum period), why some individuals are more susceptible than others to PPD, and what antidepressant treatments are effective and why. The working hypothesis for this line of inquiry is that PPD is caused by the dramatic decline in reproductive hormones that occurs just after childbirth. Specific Aim 1 outlines a series of experiments designed to evaluate the construct and face validity of a postpartum-steroid hormone withdrawal model of PPD. Anhedonia, or the loss of ability to experience pleasure, is a core feature of PPD. Thus, the effects of postpartum hormone withdrawal following hormone-simulated pregnancy will be evaluated using an intracranial self-stimulation procedure, to reveal changes in the brain "reward system" that underlie hedonic processes. Specifically, whether postpartum hormone withdrawal produces anhedonia, as measured by an increase in reward threshold in rats responding for electrical brain stimulation, will be determined. The results of this experiment will be compared to those obtained with other assays commonly used to model depression-like (forced swim test) and anxiety-like (elevated plus-maze) behaviors in rats, to determine whether post-partum hormone withdrawal also produces other psychopathological states known to be associated with PPD. Hormone withdrawal-induced changes in spontaneous locomotor activity also will be evaluated, to determine whether changes in other behaviors specifically reflect development of a "psychopathological state", or could be secondary to changes in general activity. The time course of each change in behavior, as well as changes in plasma steroid hormone levels will be determined. Specific Aim 2 will evaluate the predictive validity of the proposed PPD model by attempting to prevent postpartum hormone withdrawal-induced depression- and anxiety-like behaviors with either antidepressant or ovarian steroid treatment. Findings from the proposed model will enhance our understanding of the etiology of PPD and possibly lead to improved treatment options.
Funding Period: 2005-01-24 - 2007-12-31
more information: NIH RePORT
- Forced swim test behavior in postpartum ratsR M Craft
Department of Psychology, Washington State University, Pullman, WA 99164 4820, USA
Pharmacol Biochem Behav 96:402-12. 2010....
- Anhedonia in postpartum ratsBrittany M Navarre
Department of Psychology, Washington State University, Pullman, WA, 99164 4820, USA
Physiol Behav 99:59-66. 2010..In contrast, females that have undergone actual pregnancy are less likely to show this effect, suggesting that postpartum hormonal changes other than the dramatic decline in estradiol may buffer its negative mood effects...