Early-life FGF2 regulates developmental anxiety responses in rats bred for differences in their response to novelty

Maras PM, Turner CA, Litvin Y, Blandino P, Watson SJ, McEwen BS, Akil H
Society for Neuroscience. 2013.


Evidence suggests that the development of many emotional disorders is strongly influenced by genetic factors. Using rats that have been selectively bred for their locomotor response to novelty, we have developed two contrasting genetic backgrounds that differ in their emotional temperament: rats bred for high locomotor responses to a novel environment (bHRs) exhibit low levels of anxiety, whereas rats bred for low responses to novelty (bLRs) exhibit high levels of anxiety. We have recently shown that administration of the fibroblast growth factor 2 (FGF2) early in life is sufficient to decrease anxiety-related behavior in bLR rats when tested in adulthood, suggesting that FGF2 plays an organizing role in emotional brain function. The goal of the current study was to determine whether neonatal FGF2 alters anxiety levels earlier in development (i.e., prior to weaning). As an index of anxiety-like state in infant rats, we focused on vocalization responses to maternal separation, a potent developmental stressor that is associated with an increased emission of 40-kHz ultrasonic vocalizations (USVs). To test how early-life FGF2 modulates these distress calls, we gave FGF2 (20 ng/g) on postnatal day 1 (PND1) and quantified the number of 40-kHz USVs emitted during a five-minute isolation procedure on PND11. In vehicle-treated controls, bHRs emitted fewer USVs than bLRs, consistent with the differential anxiety phenotypes associated with the breeding lines. Moreover, FGF2 administration decreased the number of distress calls specifically in bLRs, suggesting that early-life FGF2 can shift anxiety responses in normally highly anxious bLRs. To identify the underlying mechanisms regulating developmental anxiety, ongoing studies are examining mRNA expression patterns (using in situ hybridization) of various members of the FGF gene family across development (PND2, 7, 14, 21) in bHRs and bLRs, as well as how these expression profiles are altered by early-life FGF2 administration. Together, these studies may identify critical windows of development during which the ‘anxiety temperament’ is determined, as well as potential targets for shifting that temperament.