Translational relevance of rodent models of hypothalamic-pituitary-adrenal function and stressors in adolescence

Abstract

Elevations in glucocorticoids that result from environmental stressors can have programming effects on brain structure and function when the exposure occurs during sensitive periods that involve heightened neural development. In recent years, adolescence has gained increasing attention as another sensitive period of development, a period in which pubertal transitions may increase the vulnerability to stressors. There are similarities in physical and behavioural development between humans and rats, and rats have been used effectively as an animal model of adolescence and the unique plasticity of this period of ontogeny. This review focuses on benefits and challenges of rats as a model for translational research on hypothalamic-pituitary-adrenal (HPA) function and stressors in adolescence, highlighting important parallels and contrasts between adolescent rats and humans, and we review the main stress procedures that are used in investigating HPA stress responses and their consequences in adolescence in rats. We conclude that a greater focus on timing of puberty as a factor in research in adolescent rats may increase the translational relevance of the findings.

Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose

“…Puberty occurs during adolescence but the two terms are not interchangeable as puberty involves a series of biological changes that happen during the adolescent period (Spear 2000). Adult-like gonadotropin cycling is first evident on about PD 28 (Ojeda and Urbanski 1994); whereas, vaginal opening is typically observed by PD 35, and balanopreputial separation occurs in male rats at approximately PD 40 (for reviews, see McCormick and Mathews 2007; McCormick et al 2017). With the aid of these pubertal guideposts, adolescence is usually defined as a time roughly between PD 28 and PD 55 or PD 59 (Smith 2003; Frantz et al 2006; Caster et al 2007; McCormick and Mathews 2007), while the preadolescent period occurs between weaning (PD 21) and adolescence (Romeo et al 2016).…”

Age‐dependent regulation by androgens of gene expression in the anterior hypothalamus and stress‐induced release of adrenal hormones in adolescent and adult male rats

“…Adolescence in male rats spans from approximately postnatal day (P) 28 to P59, with physical markers of pubertal onset evident at approximately 40‐42 days of age . Functional changes in hypothalamic‐pituitary‐adrenal (HPA) responses to stressors during adolescence are well‐documented in rats, although most research has involved pre‐pubertal adolescents .…”

Adolescent CB1 receptor antagonism influences subsequent social interactions and neural activity in female rats

“…Likewise, differences in the effects of AM251 administration between males and females may involve differences in the timing of puberty between the sexes. The onset of puberty in female Long‐Evans rats is typically around post‐natal day 32‐38, significantly earlier than pubertal onset in Long‐Evans males (post‐natal days 42‐48; reviewed in McCormick, Green, & Simone, 2017). As such, female rats in the current study would have been subjected to AM251 for a greater duration of this critical developmental stage compared with their male counterparts.…”