The importance of incorporating both sexes and embracing hormonal diversity when conducting rodent behavioral assays

Abstract

Reproductive hormones such as estrogens, androgens, progesterone, and others are responsible for the regulation of countless body functions in addition to their well-known control over reproductive function and behavior. The list of processes governed by internal hormonal secretions is extensive and, as such, hormonal fluctuations influence how animals perform on many established behavioral measures. Additionally, their pervasive impact can alter the way that non-hormonal drug treatments act across individuals. Male reproductive hormones are relatively stable for most of the young adult life span, and, because of this, males tend to demonstrate less variability in behavioral and physiological assessments. This stability is tempting to focus upon when investigating the behavioral effects of a new therapeutic; however, it has become increasingly clear that the effects of pharmaceutical and other manipulations can depend on the background hormone milieu of the individual. Understanding interactions with hormones is vital for the optimization of any potential or existing therapeutic and, therefore, the inclusion of measures outlined in this chapter should be considered when designing rodent behavior studies for this purpose. This chapter discusses the reproductive system and hormonal profiles of male and female rodents, how these hormonal profiles impact commonly used behavioral evaluations, and techniques for monitoring and manipulating these hormone levels, to produce optimal behavioral assessments in rodents.