Nasal epithelial cells expressing oxytocin receptor are involved in volatilized oxytocin effects on biased and social motivations and stress-declined neural stem cell proliferation

The underpinnings how nasal oxytocin (OXT) treatment may affect brain-controlled motivations and behaviors remain scarcely explored. This study was undertaken to assess the presence of volatilized OXT exposure and its rapid effects in altering motivational behaviors and stress-dampened neural stem cell proliferation. Heterozygous Venus knock-in (OXTR Venus-Neo/+) mice designed for locating oxytocin receptor (OXTR)-neurons and oxytocin receptor knockout (KO) mice were used to identify nasal epithelial OXTR-expressing neurons. We demonstrated mice' nasal epithelium harbored OXTR-expressing neurons. Volatilized OXT exposure caused a heightened Fos expression in epithelium, main olfactory bulb mitral cells, piriform cortex (PIR) and cortical amygdala (CA). Mice displayed sex-dimorphic differences in their volatilized OXT-zone choice behaviors. Lavage with a oxytocin receptor antagonist prevented volatilized OXT-produced zone preference in male mice. Volatilized OXT exposure rendered male mice' rapid decreases in active approach and investigation. Inactivating CA-projecting mitral glutamatergic neuron seemed to prevent these decreases. Volatilized OXT presentation prevented tandem stressors-induced decrease in dorsal dentate gyrus (dDG) neural stem cell proliferation. Such OXT effect was not noted in mice with oxytocin receptor KO and PIR-dCA3 circuit ablation and inhibition. Finally, tandem stressors produced a rapid decline in dCA3 cytoplasmic phosphorylated signal transducer and activator of transcription 5 (pSTAT5) levels, while volatilized OXT prevented these changes. Such volatilized OXT-produced protection was prevented by intra-dCA3 STAT5 phosphorylation inhibitor infusion. These findings prompt us to conclude nasal epithelial OXTR-expressing neurons may be involved the encoding of volatilized OXT and its rapid motivation-altering effects and neural stem cell's stress responses.