Divergent Neuroactive Steroid Responses to Stress and Ethanol in Rat and Mouse Strains: Relevance for Human Studies

The document reviews the effects of stress and ethanol on neuroactive steroids in rats, mice, and humans, emphasizing the role of these steroids in modulating the hypothalamic-pituitary-adrenal (HPA) axis. It reports that acute stress increases neuroactive steroids in rats and humans, aiding in HPA axis regulation, while in C57BL/6J mice, stress decreases neurosteroidogenesis and has excitatory effects on the HPA axis. Chronic stress leads to HPA axis adaptations and altered neuroactive steroid responses in both rats and mice. Ethanol exposure affects neuroactive steroid levels differently across species; in rats, moderate ethanol doses increase plasma and brain levels of neuroactive steroids, while in mice and humans, the responses vary due to genetic differences. Alcoholics show decreased neuroactive steroid levels during withdrawal, which normalize upon recovery. Genetic variations, such as those in the OPRM1 gene and steroid metabolism enzymes, influence the risk of alcohol dependence and the response to treatments like naltrexone. The document concludes that understanding these genetic variations is crucial for the therapeutic application of neuroactive steroids, considering human genetic diversity. The review does not specify the number of subjects in the referenced studies.