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oxytocin in PBS indicating that the nanoparticle may be used as an alternative brain delivery 37 system. We showed that oxytocin has sex-specific effects on social investigation, body mass, 38 sedation, and the oxytocin system. In contrast, similar effects were observed in both sexes in 39 neurogenesis and plasma 17β-estradiol. Our work suggests that sex differences in oxytocin 40 regulation of brain endpoints is region-specific (hypothalamus versus hippocampus) and that 41 oxytocin does not promote social investigation in females. 42 large molecules through the adsorptive-mediated transcytosis mechanism (Lu, 2012; Ovensa 89 Inc., 2018). Therefore, in the present study we compared the effects of systemic oxytocin with 90 and without the nanoparticle TRIOZAN TM . 91The objective of this study was to investigate whether systemic oxytocin delivered in 92 vehicle or with a nanoparticle drug delivery platform (TRIOZAN TM ) regulates social 93 investigation, oxytocin levels in the brain and periphery, oxytocin-immunoreactive cells in the 94 hypothalamus (SON and PVN) and adult hippocampal neurogenesis in male and female rats. We 95 hypothesized that oxytocin would impact the sexes differentially and that TRIOZAN TM would 96 increase delivery of oxytocin to the brain and result in enhanced effects on social investigation 97 and hippocampal neurogenesis. 98 99 Materials and Methods 100 Animals and treatments 101Adult male and female Sprague-Dawley rats (n=5-8/treatment/sex; 60 days old and 102 tested around 80 days old) were obtained from Charles River (Quebec, Canada) and double-103 housed with food and water available ad libitum. All protocols were approved by the 104 Institutional Animal Care Committee at the University of British Columbia and conformed to the 105 guidelines set out by the Canadian Council for Animal Care. Ten days after arrival, males and 106 females were randomly divided into one of the following treatment groups: oxytocin in 0.1 M 107 PBS (0.5 or 1.0 mg/kg), oxytocin delivered in TRIOZAN TM (0.5 or 1.0 mg/kg, prepared by PO-108

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