Early life FGF2 treatment alters vasopressin and oxytocin gene expression in animals that differ in their response to novelty

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


Selectively bred high responder rats (bHRs) exhibit high levels of locomotor activity in response to a novel environment and low levels of anxiety-like behavior. Conversely, selectively bred low responder rats (bLRs) exhibit low levels of novelty-induced locomotion and high levels of anxiety-like behavior. Previously, we found that administration of fibroblast growth factor-2 (FGF2) early in life can decrease anxiety-related behavior in the highly anxious bLRs when tested as adults. However, the mechanism for this effect has not been fully explored. Activation of the oxytocin receptor (OTR) is known to have anxiolytic effects, while activation of the vasopressin receptor 1A (AVPR1A) has anxiogenic effects. Therefore, we wondered whether early life FGF2 treatment (20ng/g, s.c.) on postnatal day 1 (PND1) would have an effect on gene expression of the oxytocin and vasopressin receptors in adulthood. To this end, we measured gene expression by mRNA in situ hybridization. bHRs had more OTR gene expression in the ventromedial hypothalamus than bLRs. Conversely, bLRs had more AVPR1A gene expression in the central amygdala than bHRs. Strikingly, neonatal FGF2 normalized mRNA levels of both receptors in bLRs, making their gene expression more bHR-like. We are currently exploring gene expression patterns of OTR and AVPR1A at earlier developmental time points, as well as protein levels. Taken together, the results suggest that the highly anxious bLRs can benefit from early life FGF2 treatment in terms of their oxytocin and vasopressin gene expression.