administration of OXT has been shown to induce Fos expression in OXT neurons in the PVN (Carson et al., 2010b, Leong et al., 2017), suggesting that peripheral administration may induce endogenous central release. In a recent study, Smith et al., (2019) reported detectable concentrations of OXT in amygdala and hippocampus of OXT null mice following both intranasal and intraperitoneal administration of the neuropeptide. These data validate that the source of measured OXT originates solely from exogenous administration, as the genetically deficient (knockout) mice do not produce endogenous OXT. However, Lee et al. (2018) demonstrated that while OXT administered through intranasal and intravenous routes of administration increased OXT levels in cerebral spinal fluid, it did not activate a feed forward mechanism to elevate endogenous OXT. Thus, while studies are largely consistent regarding elevated OXT in the CNS following peripheral administration, the mechanism by which exogenous OXT delivered in the periphery activates OXT signaling in the brain remains unclear. Further studies are needed to address this issue, as it is relevant to the potential for OXT to serve as a therapeutic for alcohol/drug addiction.
