Neuroendocrine and neuroimmune responses in male and female rats: evidence for functional immaturity of the neuroimmune system during early adolescence.

Adolescence is a developmental period characterized by rapid behavioral and physiological changes, including enhanced vulnerability to stress. Recent studies using rodent models of adolescence have demonstrated age differences in neuroendocrine responses and blunted neuroimmune responding to pharmacological challenges. The present study was designed to test whether this neuroimmune insensitivity would generalize to a non-pharmacological stress challenge. Male and female adolescent (P29-33) and adult (P70-80) Sprague Dawley rats were exposed to intermittent footshock for one-, two-, or two-hours + recovery. Plasma corticosterone and progesterone levels as well as gene expression of several cytokines and c-Fos gene expression in the paraventricular nucleus of the hypothalamus (PVN), the medial amygdala (MeA), and the ventral hippocampus (vHPC) were analyzed. The results of the present study demonstrated differences in response to footshock, with these differences dependent on age, sex, and brain region of interest. Adult males and females demonstrated time-dependent increases in IL-1β and IL-1R2 in the PVN, with these changes not evident in adolescent males and substantially blunted in adolescent females. TNFα expression was decreased in all regions of interest, with adults demonstrating more suppression relative to adolescents and age differences more apparent in males than in females. IL-6 expression was affected by footshock predominantly in the vHPC of adolescent and adult males and females, with females demonstrating prolonged elevation of IL-6 gene expression. In summary, central cytokine responses to acute stressor exposure are blunted in adolescent rats, with the most pronounced immaturity evident for the brain IL-1 signaling system.