The inner dynamics of positive human-animal interactions: Investigating the roles of oxytocin, opioids, dopamine, serotonin and the proteome

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 obtained cerebrospinal fluid samples 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. Additionally, the duration and frequency of physical contacts initiated by the pig toward the human were coded from videos. The test condition (human familiarity × contact type) had a significant effect on the concentration of β-endorphin (F_1118.59 = 4.45; P = 0.04) and 5-HIAA (F_1,73.47 = 5.02; P = 0.03), and tended to affect the concentration of OT (F_{1, 119.8} = 3.19; P = 0.08) and DOPAC (F_1,70.57 = 3.31; P = 0.07), but pairwise comparisons were not significant or showed complex changes. Specifically, OT was highest when the unfamiliar humans ignored the pig compared to when they delivered positive contacts (t_70.6 = 3.31; P = 0.008), and β-endorphin tended to be higher after interacting with the familiar human compared to the unfamiliar humans (60 min post-test; t_37.9 = 3.3; P = 0.055). There were only minor differences in the pigs' behaviour, suggesting that pigs seemed to perceive all test conditions as positive. Nevertheless, β-endorphin and OT appear to relate to different aspects of the interactions, possibly familiarity vs. novelty respectively.