Maternal-offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric, and
neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well understood. Our hypothesis is that
allopregnanolone, during gestation, plays a particularly vital role in mitigating effects of stress on the developing fetus and may mediate, in part, alterations apparent throughout the lifespan. Specifically, altered balance between
glucocorticoids and
progestogens during critical periods of development (stemming from psychological, immunological, and/or endocrinological stressors during gestation) may permanently influence behavior, brain morphology, and/or neuroendocrine-sensitive processes. 5α-reduced
progestogens are integral in the developmental programming of sex-typical, stress-sensitive, and/or disorder-relevant phenotypes. Prenatal stress (PNS) may alter these responses and dysregulate
allopregnanolone and its normative effects on stress axis function. As an example of a neurodevelopmental, neuropsychiatric, and/or neurodegenerative process, this review focuses on responsiveness to
drugs of abuse, which is sensitive to PNS and progestogen milieu. This review explores the notion that
allopregnanolone may effect, or be influenced by, PNS, with consequences for neurodevelopmental-, neuropsychiatric-, and/or neurodegenerative- relevant processes, such as addiction.