Can animal models resemble a premenstrual dysphoric condition?

The onset of symptoms of Premenstrual Disorders is associated mainly with abnormal levels of progesterone and its metabolite 5a-reduced, Allopregnanolone (ALLO), during the late luteal phase of the menstrual cycle of vulnerable women. These abnormalities may be related to rapid fall of ALLO (Lovick et al. 2017), alterations in the function of the enzymatic system involved in the conversion of progesterone to ALLO (Klatzin 2006;b; Martinez et al. 2016), or GABAA receptor subunit composition that in consequence, affects its functionality in the brain (Bixo et al. 2018; Gingell et al. 2012; Liu et al. 2015; Toffoletto et al. 2014). Animal models of PMD have been developed using rodents' estral cycle as a skill to evaluate signs of anxiety, aggressive or depressive-like behaviors as an index of core symptoms and study some components of the neurobiology of PMD. In these studies, it has been possible to detect high levels of anxiety-, aggressive-, and depressive-like behavior in rodents on diestrus-II phase, when progesterone falls rapidly and represents the abrupt drop of progesterone observed in the late luteal phase of the menstrual cycle of women with PMD. On the other side, ALLO has been involved in the turn-off of the hypothalamus–pituitaryadrenal (HPA) axis in response to stress (Purdy et al. 1991). Therefore, if ALLO levels differ in women with PMD, its HPA axis regulation may be insufficient. Further, stress and ALLO contribute to modulating GABAA receptor function in several brain areas such as the hippocampus, amygdala, and prefrontal cortex, which regulate anxiety, aggression, and depression, symptoms of PMD. From animal models emerge the hypothesis that changes in the GABAA receptor subunit composition could be a key target to understand PMD neurobiology and develop treatment strategies. [Display omitted] •Premenstrual Disorders (PMD) can disrupt women's lives.•Synthesis, metabolism, and target sites of progesterone and allopregnanolone are involved in PMD.•HPA-axis is involved in the pathology.•Alterations on GABAA subunits receptors composition are associated with PMD.•Animal models based on behavior and hormonal manipulations provide a tool for the study of PMD. Around 80% of women worldwide suffer mild Premenstrual Disorders (PMD) during their reproductive life. Up to a quarter are affected by moderate to severe symptoms, and between 3% and 8% experience a severe form. It is classified as premenstrual syndrome (PMS) with predominantly physical