DNA damage after chronic oxytocin administration in rats: a safety yellow light?

Abstract

Adjuvant therapy is a common therapeutic strategy used for schizophrenia management. Oxytocin has shown promising results as antipsychotic adjuvant in patients with schizophrenia. Although short-term clinical studies have indicated tolerability and no major side-effect manifestation, long-term studies remain needed. In this study, we investigated whether oxytocin chronic administration in rats may lead to brain DNA damage by comet assay. Our results suggest that 21 and 56-day treatment with once daily intraperitoneal oxytocin (0.1, 1.0 and 10.0 mg/kg) may cause substantial DNA damage in hippocampus. We have not found differences on body weight gain. Our findings also point that further clinical and preclinical studies evaluating oxytocin safety after chronic exposure are necessary.

Infrequent Intranasal Oxytocin Followed by Positive Social Interaction Improves Symptoms in Autistic Children: A Pilot Randomized Clinical Trial

“…However, there is no empirical support for this treatment strategy and G protein-coupled receptors exhibit rapid desensitization and downregulation following exogenous treatment with agonist ligands [31,32]. Chronic/ daily OXT treatment leads to extensive OXTR and vasopressin-1A receptor downregulation in the rat forebrain [33][34][35][36]. Additionally, when OXT binds to its receptor it can differentially recruit intracellular G protein-coupled pathways with increasing OXT bioavailability shifting coupling away from the excitatory Gq protein to the inhibitory Gi one [37][38][39].…”

Chronic oxytocin administration as a tool for investigation and treatment: A cross-disciplinary systematic review

“…On the other hand, chronic OT contributed to DNA damage in the rat hippocampus by increasing oxidative stress over extended periods of treatment (e.g., 21 days). These mixed findings warrant future research on the long-term safety of chronic OT (Leffa et al, 2017). Mechanistic research on chronic OT's anti-inflammatory properties is furthermore needed, especially in terms of the indirect pathways by which OT modulates inflammation (e.g., via suppression of the HPA-axis) (Peters et al, 2014).…”

“…Chronic OT can induce weight loss in animals through physiological and neural mechanisms that increase the time between feedings and suppress food-related reward (Altirriba et al, 2015;Arletti et al, 1989;Blevins et al, 2015;Morton et al, 2012). In contrast, chronic OT may not be an effective weight-loss intervention for non-obese or slow-to-grow animals (Balazova et al, 2016;Leffa et al, 2017;Uvnäs-Moberg et al, 1996).…”

Infrequent intranasal oxytocin followed by positive social interaction improves symptoms in autistic children: a pilot randomized clinical trial

“…It is well established that G proteincoupled receptors exhibit rapid desensitization, internalization and subsequent down-regulation following exogenous treatment with agonist ligands [32], including the OXTR [33][34][35][36]. Indeed, chronic/daily OXT treatment leads to extensive OXTR and vasopressin-1A receptor down regulation in the rat forebrain [34][35][36] and may even cause DNA damage in the hippocampus [37]. Additionally, when OXT binds to its receptor it can recruit different intracellular G protein-coupled pathways resulting in opposite effects on neuronal activity in a concentration-dependent manner, with increasing OXT bioavailability shifting coupling away from the excitatory Gq-protein to the inhibitory Gi-one [38][39][40].…”

“…However, there is no empirical support for this treatment strategy and G protein-coupled receptors exhibit rapid desensitization and down-regulation following exogenous treatment with agonist ligands [32]. Chronic/daily OXT treatment leads to extensive OXTR and vasopressin-1A receptor down-regulation in the rat forebrain [33][34][35][36]. Additionally, when OXT binds to its receptor it can differentially recruit intracellular G protein-coupled pathways with increasing OXT bioavailability shifting coupling away from the excitatory Gq-protein to the inhibitory Gi-one [37][38][39].…”