Methods and considerations for the use of hormonal contraceptives in rat models of neurobehavior

Hormonal contraceptives (HCs), prescribed to millions of women around the world, alter the ovarian hormonal cycle resulting in neurobehavioral changes in HC users. Human epidemiological and experimental data has characterized some of these effects with oftentimes conflicting or irreproducible results, reflecting a dearth of research considering different compositions, routes of administration, or time-courses of HC use. Non-human animal research can model these effects and help elucidate the underlying mechanisms by which different HCs modulate neurobehavioral outcomes. Still, animal models using HCs are not well-established. This may be because the pharmacological profile of HCs - including the metabolism, receptor binding affinity, and neuromodulatory effects - is dynamic and not always clearly translatable between animals and humans. The current review addresses these issues and provides basic methods and considerations for the use of HCs in animal models of neurobehavior to help advance the field of behavioral neuroendocrinology and inform decisions regarding to women's health.