Although further studies are required to elucidate the mechanistic role of NRG3 in neurocognitive and neuropsychiatric disorders, the present results provide independent support for 1) previous associations of NRG3 genetic variation to cognitive and behavioral phenotypes in humans; 2) present novel evidence that NRG3 impacts early neonatal brain development where it influences circuitry involved in behaviors related to anxiety and sociability and 3) highlight an experimental rodent model for examining the developmental effects of neurotrophin exposure as it relates to clinical brain disorders. Here we provide novel evidence, that peripherally injected NRG3 can cross the BBB of neonatal mice, and that Tofacitinib overexposure to NRG3 during early postnatal life leads to alterations in anxietylike and social behaviors in adulthood. These data demonstrate the relevance of NRG3 in normal brain development and function, and provide initial insight into how altered NRG3 signaling may be pathophysiologically relevant to neuropsychiatric and neurodevelopmental disorders. The dose of 3 mg/kg NRG3 had no effects on mortality, weight, neurodevelopmental milestones or general health measures. However, in agreement with previous studies of neonatal overexposure to NRG1 and other epidermal growth factors, we identified that NRG1 exposure stimulates precocious eye opening and tooth eruption. These results suggest while 3-fold higher than NRG1, the dose of NRG3-EGF given was well tolerated and subsequent behavioral changes were CNS driven rather than a peripheral effect. The peripheral effects observed in neonatally administered NRG1 mice is likely due to NRG1’s widespread expression and function in multiple organ systems including the heart, breast and nervous system. Conversely, NRG3 expression is neuronally enriched and therefore its actions are likely more restricted to the brain. Moreover, the EGF domains of NRG1 and NRG3 share only 31% sequence homology and therefore it is probable some of their biological actions are distinct. Non-redundancy between the growth factors is further evidenced by our findings that the behavioral consequences of neonatal overexposure to NRG3 are non-overlapping with that of overexposure to NRG1. For example, while NRG1 overexposure in neonates has been previously demonstrated to induce increased sensitivity to the locomotor effects of amphetamine, we present evidence that at 3 mg/kg amphetamine induced locomotor activity is enhanced to the same extent in vehicle and NRG3EGF overexposed mice.