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.
Similar content being viewed by others
References
Averbeck BB, Bobin T, Evans S, Shergill SS (2012) Emotion recognition and oxytocin in patients with schizophrenia. Psychol Med 42:259–266. doi:10.1017/S0033291711001413
Biyikli NK, Tuğtepe H, Sener G, et al. (2006) Oxytocin alleviates oxidative renal injury in pyelonephritic rats via a neutrophil-dependent mechanism. Peptides 27:2249–2257. doi:10.1016/j.peptides.2006.03.029
Boer GJ (1993) Chronic oxytocin treatment during late gestation and lactation impairs development of rat offspring. Neurotoxicol Teratol 15:383–389
Boyda HN, Tse L, Procyshyn RM, et al. (2010) Preclinical models of antipsychotic drug-induced metabolic side effects. Trends Pharmacol Sci 31:484–497. doi:10.1016/j.tips.2010.07.002
Bujanow W (1972) Hormones in the treatment of psychoses. Br Med J 4:298
Bujanow W (1974) Letter: is oxytocin an anti-schizophrenic hormone? Can Psychiatr Assoc J 19:323
Collins AR (2004) The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol 26:249–261. doi:10.1385/mb:26:3:249
Collins A, Dusinská M, Franklin M, et al. (1997) Comet assay in human biomonitoring studies: reliability, validation, and applications. Environ Mol Mutagen 30:139–146
Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 17:1195–1214. doi:10.1096/fj.02-0752rev
Feifel D, Reza T (1999) Oxytocin modulates psychotomimetic-induced deficits in sensorimotor gating. Psychopharmacology 141:93–98
Feifel D, Macdonald K, Nguyen A, et al. (2010) Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients. Biol Psychiatry 68:678–680. doi:10.1016/j.biopsych.2010.04.039
Gimpl G, Fahrenholz F (2001) The oxytocin receptor system: structure, function, and regulation. Physiol Rev 81:629–683
Huang H, Michetti C, Busnelli M, et al. (2014) Chronic and acute intranasal oxytocin produce divergent social effects in mice. Neuropsychopharmacology 39:1102–1114
Iqbal Z, Rahman Z, Muhammad F, et al. (2013) Oxytocin induced oxidative stress in lactating Bubalis Bubalis (Nili Ravi. BMC Vet Res 9:169. doi:10.1186/1746-6148-9-169
Ito T, Ando H, Suzuki T, et al. (2010) Identification of a primary target of thalidomide teratogenicity. Science 327:1345–1350. doi:10.1126/science.1177319
Kuehn BM (2011) Scientists probe oxytocin therapy for social deficits in autism, schizophrenia. JAMA 305:659–661. doi:10.1001/jama.2011.117
Lee S-Y, Park S-H, Chung C, et al. (2015) Oxytocin protects hippocampal memory and plasticity from uncontrollable stress. Sci Rep 5:18540. doi:10.1038/srep18540
Lepping P, Delieu J, Mellor R, et al. (2011) Antipsychotic medication and oxidative cell stress: a systematic review. J Clin Psychiatry 72:273–285. doi:10.4088/JCP.09r05268yel
Leucht S, Heres S, Kissling W, Davis JM (2011) Evidence-based pharmacotherapy of schizophrenia. Int J Neuropsychopharmacol 14:269–284. doi:10.1017/S1461145710001380
Mairesse J, Gatta E, Reynaert ML, Marrocco J, Morley-Fletcher S, Soichot M, Deruyter L, Camp GV, Bouwalerh H, Fagioli F, Pittaluga A, Allorge D, Nicoletti FMS (2015) Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats. Psychoneuroendocrinology 62:36–46. doi:10.1016/j.psyneuen.2015.07.00
Miyamoto S, Miyake N, Jarskog LF, et al. (2012) Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents. Mol Psychiatry 17:1206–1227. doi:10.1038/mp.2012.47
Moraes MCS, Neto JBC, Menck CFM (2012) DNA repair mechanisms protect our genome from carcinogenesis. Front Biosci 17:1362–1388
Neumann ID, Slattery D (2016) Oxytocin in general anxiety and social fear: a translational approach. Biol Psychiatry 79:213–221. doi:10.1016/j.biopsych.2015.06.004
Pedersen CA, Gibson CM, Rau SW, et al. (2011) Intranasal oxytocin reduces psychotic symptoms and improves theory of mind and social perception in schizophrenia. Schizophr Res 132:50–53. doi:10.1016/j.schres.2011.07.027
Peters S, Slattery D, Uschold-Schmidt N, et al. (2014) Dose-dependent effects of chronic central infusion of oxytocin on anxiety, oxytocin receptor binding and stress-related parameters in mice. Psychoneuroendocrinology 42:225–236. doi:10.1016/j.psyneuen.2014.01.021
Sánchez JPB, Ellenbroek BA (2016) Preclinical Effects of Antipsychotic Drugs. Curr Top Behav Neurosci. doi:10.1007/7854_2016_447
Simsek Y, Celik O, Karaer A, et al. (2012) Elevated cardiac oxidative stress in newborn rats from mothers treated with atosiban. Arch Gynecol Obstet 285:655–661. doi:10.1007/s00404-011-2069-5
Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191
Souza RP, de Luca V, Meltzer HY, et al. (2010) Schizophrenia severity and clozapine treatment outcome association with oxytocinergic genes. Int J Neuropsychopharmacol 13:793–798. doi:10.1017/S1461145710000167
Szeto A, Nation DA, Mendez AJ, et al. (2008) Oxytocin attenuates NADPH-dependent superoxide activity and IL-6 secretion in macrophages and vascular cells. Am J Physiol Endocrinol Metab 295:E1495–E1501. doi:10.1152/ajpendo.90718.2008
Tice RR, Agurell E, Anderson D, et al. (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206–221
Acknowledgments
Prostricto/UNESC, PIBIC/UNESC/CNPq and Universal CNPq (484972/2011-1).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Leffa, D.D., Daumann, F., Damiani, A.P. et al. DNA damage after chronic oxytocin administration in rats: a safety yellow light?. Metab Brain Dis 32, 51–55 (2017). https://doi.org/10.1007/s11011-016-9885-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-016-9885-z