The Transcriptional Signature of a Runner’s High

Introduction Endorphins, endocannabinoids, monoamines, and neurotrophins have all been implicated in the euphoric response to endurance running, known as a runner's high. The epi-transcriptional mechanisms regulating this effect have not been defined. Here, we investigate peripheral micro-ribonucleic acid (miRNA) changes unique to athletes experiencing post-run euphoria, yielding insights about gene networks that control a runner's high. Methods A cohort study involving 25 collegiate runners (48% female, age = 20±1 years) examined salivary RNA levels before and after a long-distance run. Participants were divided into runner's high (RH) and non-runner's high (NRH) groups based on surveys of four criteria (mood, lost sense of time, run quality, and euphoria). Physiologic measures were also recorded (temperature, heart-rate, blood pressure, pupillary dilatation, salivary serotonin). Levels of miRNAs and their mRNA targets were compared across pre/post-run samples from RH and NRH groups with two-way analysis of variance. Representation of opioid, gamma-aminobutyic acid (GABA), endocannabinoid, neurotrophin, serotonergic, and dopaminergic pathways was assessed in DIANA miRPath. Pearson's correlation analyses examined relationships between miRNAs and runner's high indices. Results RH participants (n=13) demonstrated post-run mydriasis (p=0.046) and hypothermia (p=0.043) relative to NRH participants (n=12), but had no difference in serotonin dynamics (p=0.88). Six miRNAs (miR-194-5p, miR-4676-3p, miR-4254, miR-4425, miR-1273-3p, miR-6743-5p) exhibited significant effects (FDR

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