Social Instability in Adolescence Alters the Central and Peripheral Hypothalamic‐Pituitary‐Adrenal Responses to a Repeated Homotypic Stressor in Male and Female Rats

Abstract

There has been little research on effects of chronic stressors on neuroendocrine function in adolescence despite increasing evidence of enduring effects of stressors during this period on behaviour in adulthood. We previously reported that social stress (SS: daily 1 h isolation and new cage partner for 16 days) in adolescence altered locomotor responses to psychostimulants in adulthood. Here, we investigated neuroendocrine responses over the duration of the procedure that may underlie the enduring effects of SS. SS rats were compared to rats undergoing daily isolation only (ISO) and controls (CTL) to determine responses to acute and repeated isolation with and without social instability. At 30 days of age (first isolation), higher plasma corticosterone and corticotrophin-releasing hormone (CRH) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus and in the central nucleus of the amygdala (CeA) were found in males caged with a new partner (SS) after isolation than those returned to their original partner (ISO). On day 45, SS males and females showed less habituation (higher bioactive levels of corticosterone based on plasma corticosterone and corticosteroid binding globulin levels) to the 16th episode of isolation than did ISO. SS and ISO had higher baseline expression of CRH mRNA in the PVN on day 45 than did CTL, and only CTL had increased levels after isolation. CRH mRNA expression in the CeA increased to a first isolation in CTL and to a 16th isolation in SS but not in ISO males. Modest differences in social interactions were observed between SS and ISO when returned to their cages after isolation. The results suggest that mild social stressors in adolescence impede neuroendocrine adaptation to homotypic stressors. The resultant increase in exposure to glucocorticoids over adolescence may alter ongoing brain development and increase vulnerability to psychopathology.

Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats

“…This contrasts with previous reports of increased anxiety (Giovanoli et al, 2013;Jacobson-Pick et al, 2008;Maslova et al, 2002aMaslova et al, , 2002bTsoory et al, 2007;Yee et al, 2011), although negative or inconsistent results have also been reported (Avital and Richter-Levin, 2005;Bourke and Neigh, 2011;Jacobson-Pick and Richter-Levin, 2010;McCormick et al, 2007;Peleg-Raibstein and Feldon, 2011;Pohl et al, 2007;Toledo-Rodríguez and Sandi, 2007). This is likely related to a differential susceptibility to stress among the different strains of rats and mice used (e.g., Maslova et al, 2002aMaslova et al, , 2002b.…”

Adolescence: A central event in shaping stress reactivity

“…3), it is difficult to simply correlate greater CRH cellular activity with longer hormonal responses. There are also pubertal-related changes in CRH mRNA expression in the PVN such that prepubertal males have greater basal CRH expression than adults (Romeo et al, 2007), though stressors lead to increases in CRH expression in both the juvenile and adult PVN (McCormick, Merrick, Secen, & Helmreich, 2006;Romeo et al, 2007;Viau, Bingham, Davis, Lee, & Wong, 2005). Taken together, our data suggest that differential regulation of CRH cells in the PVN may play a role in the changes in HPA reactivity during adolescence, though the exact role of this differential activation remains unclear.…”

Age- and Stress-Induced Changes in Corticotropin-Releasing Hormone mRNA Expression in the Paraventricular Nucleus of the Hypothalamus

“…The influence of acute stress on CRH expression in the prepubertal, postweaning PVN is less established. To date, only two studies to our knowledge have assessed stress-induced modulation of CRH mRNA in the prepubertal PVN [25, 30]. The study by McCormick et al [30] showed significant stress-induced increases in CRH expression in the PVN of 30-day-old males, while a study by Viau et al [25] reported a trend toward stress-induced increases in CRH mRNA in the PVN of 28-day-old males.…”