Reproductive depression can be defined as symptoms or syndromes of depression in women that are presumed to occur as side effects of reproductive function. Classic examples of reproductive depression are premenstrual syndrome and postpartum depression, which can be serious medical conditions. One etiological theory of these symptoms' states that natural withdrawal of progesterone circulation in the periphery during the ovulatory cycle or birthing process can sometimes manifest as a mental illness because the brain is responsive to changes in circulating levels of progesterone and its metabolites. The current work discusses a mouse model of this phenomenon, termed progesterone withdrawal, and employs behavioral pharmacology, pharmacological and neuroanatomical methods to advance this line of research.