Oxytocin (OXT) has therapeutic effects on psychiatric disorders, such as anxiety and depression, in both animals and humans; however, an increasing number of OXT treatment studies have reported conflicting results. Although the effects of OXT on emotion regulation vary depending on factors such as sex and dosage, the dose-dependent effects of chronic OXT administration remain unclear, particularly in women. In this study, we aimed to assess the dose-dependent effects of chronic OXT administration on emotional behavior in female mice with corticosterone (CORT)-induced anxiety and depression. A total of 58 female C57BL/6J mice received daily co-administration of OXT (0.1 or 1 mg/kg, intraperitoneal) and/or CORT (40 mg/kg, subcutaneous) for 4 weeks, and their anxiety- (open field and elevated plus maze tests) and depression-like behaviors (forced swimming and tail suspension tests) were evaluated. A 0.1 mg/kg dose of OXT blocked the CORT-induced increase in anxiety-like behavior (open field test) and depression-like behavior (forced swimming test), whereas the 1 mg/kg dose did not. Similarly, a dose-dependent effect of OXT was observed in the elevated plus maze and tail suspension tests. Furthermore, the 1 mg/kg dose of OXT significantly increased plasma OXT levels. These findings suggest that a certain level of OXT signaling activity is needed to exert anxiolytic and antidepressant-like effects, which may lead to a non-linear dose-dependent effect of OXT in a female mouse model of CORT-induced anxiety and depression. Targeting dose-dependent OXT signaling is a potential therapeutic strategy for women with psychiatric disorders.
© 2026 The Authors. Published by Elsevier B.V.

Friendships-i.e. selective peer relationships-are an important aspect of human behavior, but are rare in rodent species. Meadow voles are seasonally social rodents that form non-reproductive social groups in winter/short day lengths that are selective in nature. Across rodents, oxytocin neurons in the paraventricular nucleus (PVN) of the hypothalamus are typically active during socially salient events, including interaction with novel individuals as well as social separation. To assess whether familiar and novel peer interactions produce different patterns of immunolabeling in a species that forms bonds with familiar individuals, we measured oxytocin neuron immunoreactivity and colabeling with the immediate early gene product cFos. Oxytocin labeling and oxytocin/cFos colabeling were higher after interaction with a novel same-sex conspecific than after reunion with a peer partner. Colabeling was also high after 24 h separation without reunion. Circulating corticosterone concentrations paralleled PVN oxytocin neuron activity. We also investigated whether oxytocin signaling was photoperiod dependent and could contribute to seasonal differences in meadow vole social behavior. Oxytocin receptor densities are known to be higher in multiple brain regions in short day lengths in meadow voles, but we found no concomitant change in PVN oxytocin positive cell count. Together these studies indicate that seasonal changes in behavior correlate with oxytocin signaling at the receptor level, while short term experiences modulated oxytocin neuron activity differentially by social context.
© 2025. The Author(s).

Oxytocin, often called the "love hormone," is well-known for its roles in childbirth and lactation. Beyond these traditional functions, it plays a vital role in emotional and social behaviors, mood regulation, stress responses, and various physiological processes. Blood oxytocin levels are typically low under basal conditions but increase significantly during labor, breastfeeding, sexual activity, and positive social interactions. However, reported plasma oxytocin levels in humans and rodents vary widely across studies. In this study, we reviewed plasma oxytocin levels in rats from research conducted over the past decade, emphasizing the notable discrepancies observed between studies. Furthermore, we investigated the effects of two anesthetic protocols (inhaled isoflurane and a combination of three anesthetics) and the proteinase inhibitor aprotinin on plasma oxytocin levels in adult male rats. Our findings revealed that neither the anesthetics nor aprotinin significantly affected plasma oxytocin levels. We also discussed potential factors contributing to the marked differences in reported rat blood oxytocin levels.

Research on the neuroendocrine basis of positive interactions has predominantly focused on oxytocin (OT), although dopamine (DA) and opioids also play crucial roles. Furthermore, these neurotransmitters are known to interact with each other but have seldom been studied concurrently. In this study, we quantified longitudinal changes in these neurotransmitters using a within-subject, 2 × 2 factorial design by varying human familiarity (familiar versus unfamiliar) and contact type (positive contacts versus ignoring) for 10 min human-pig interaction sessions. We repeatedly sampled cerebrospinal fluid from 10 pigs through a spinal catheter 65 and 5 min before the test and at 10, 30, 60, 120 and 240 min after the start of the test. Samples at various timepoints were analysed for OT, DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), β-endorphin opioids concentrations, and using proteomics to explore novel protein candidates. The test condition (human familiarity × contact type) had a significant effect on the concentration of β-endorphin (F 1,118.59 = 4.45; P = 0.04) and 5-HIAA (F 1,73.47 = 5.02; P = 0.03), and tended to affect the concentration of oxytocin (F 1, 119.8 = 3.19; P = 0.08) and DOPAC (F 1,70.57 = 3.31; P = 0.07), but pair-wise comparisons were not significant. There was only a minor effect on the pigs’ behaviour, which suggests that the test conditions may have had limited effect. Nevertheless, this approach provides a valuable method to study neurotransmitter changes over time and simultaneously. Highlights - Oxytocin was higher when pigs were ignored than when they had positive contacts - Oxytocin was highest in the novel condition of an unfamiliar human ignoring the pig - Human familiarity and contact type affected β-endorphin and 5-HIAA concentrations - Dopamine metabolites and the proteome were not affected by the test conditions

Shelter environments can be inherently stressful for dogs, a highly social species that forms strong attachment bond with humans. This study evaluated stress responses in 26 shelter dogs during routine veterinary examinations, analyzing behavioral scores alongside physiological and hormonal parameters, including heart rate, body temperature, cortisol (CRT), oxytocin (OXT), serotonin (5-HT), tryptophan (TRP), and interleukin-6 (IL-6). A significant negative correlation was observed between OXT and CRT (ρ = -0.540, p = 0.007), particularly in dogs exhibiting relaxed behavior. OXT was also negatively correlated with body temperature (ρ = -0.435, p = 0.034), supporting its potential role in modulating stress-induced hyperthermia. No significant associations were found between TRP, 5-HT, IL-6, or other physiological measures and behavioral scores. The absence of correlation between TRP and 5-HT may be due to blood-brain barrier regulation, while IL-6's lack of association suggests further investigation is needed to clarify its role in canine stress responses. These findings highlight OXT's possible buffering effect on the hypothalamic-pituitary-adrenal axis and suggest that behavioral assessment may offer a more sensitive measure of canine stress than hormonal or physiological parameters alone. Future studies with larger and more diverse samples are needed to confirm and expand upon these results.