Fig. 1.

Timeline of neural development of the corticotropin-releasing factor (CRF) and dorsal raphe nucleus (dRN) serotonin systems in relation to the time periods in which different stress paradigms are employed. Note that peri-adolescence for the rat is considered to begin at weaning (PND 21), encompassing adolescence from PND 32 to PND 56–60 (although adolescence may begin later in males) (Sengupta, 2013). Rats are thought to attain puberty by PND 50 (Sengupta, 2013). The time period in which each early-life stress paradigm is indicated represents the age ranges used by a majority of studies described here, although a number of social isolation/disruption or social defeat studies use more specific age ranges to restrict stress to discrete developmental periods, as detailed in the text. CRF expression in the central nucleus of the amygdala (CeA; gray bar) is thought to increase over development, whereas CRF receptor expression (solid lines) in most brain regions peaks very early in postnatal development. As indicated by the bifurcating black solid line, CRF receptor expression shows a second developmental change over puberty, with either a decrease or increase in expression dependent on brain region studied, sex of individual and receptor (CRF₁ or CRF₂). The expression of tryptophan hydroxylase 2 (TPH2) in the dRN (dashed lines), as a measure of serotonin levels/neurons, increases over development in males, but peaks around PND42 in females and then declines to adulthood. See text for citations.