title: Chronic and acute intranasal oxytocin produce divergent social effects in mice.
abstract: Intranasal administration of oxytocin (OXT) might be a promising new adjunctive therapy for mental disorders characterized by social behavioral alterations such as autism and schizophrenia. Despite promising initial studies in humans, it is not yet clear the specificity of the behavioral effects induced by chronic intranasal OXT and if chronic intranasal OXT could have different effects compared with single administration. This is critical for the aforementioned chronic mental disorders that might potentially involve life-long treatments. As a first step to address these issues, here we report that chronic intranasal OXT treatment in wild-type C57BL/6J adult mice produced a selective reduction of social behaviors concomitant to a reduction of the OXT receptors throughout the brain. Conversely, acute intranasal OXT treatment produced partial increases in social behaviors towards opposite-sex novel-stimulus female mice, while on the other hand, it decreased social exploration of same-sex novel stimulus male mice, without affecting social behavior towards familiar stimulus male mice. Finally, prolonged exposure to intranasal OXT treatments did not alter, in wild-type animals, parameters of general health such as body weight, locomotor activity, olfactory and auditory functions, nor parameters of memory and sensorimotor gating abilities. These results indicate that a prolonged over-stimulation of a 'healthy' oxytocinergic brain system, with no inherent deficits in social interaction and normal endogenous levels of OXT, results in specific detrimental effects in social behaviors.
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Huiping
authors.initials: H
authors.lastname: Huang
authors.affiliation: 1] Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy [2] Behavioural Neuroscience Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Michetti
authors.affiliation: 1] Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milan, Italy [2] CNR, Institute of Neuroscience, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Busnelli
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Managò
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Sannino
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Scheggia
authors.affiliation: Pattern Analysis and Computer Vision, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Giancardo
authors.affiliation: Pattern Analysis and Computer Vision, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Sona
authors.affiliation: Pattern Analysis and Computer Vision, Istituto Italiano di Tecnologia, Genova, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Murino
authors.affiliation: CNR, Institute of Neuroscience, Milan, Italy.
authors.forename: Bice
authors.initials: B
authors.lastname: Chini
authors.affiliation: Behavioural Neuroscience Section, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Scattoni
authors.affiliation: 1] Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy [2] Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Padova, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Papaleo
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001307:Auditory Perception / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D055696:Olfactory Perception / Q000187:drug effects; D010121:Oxytocin / Q000008:administration & dosage*; D011619:Psychotropic Drugs / Q000008:administration & dosage*; D018045:Receptors, Oxytocin / Q000819:agonists / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects; D055139:Sensory Gating / Q000187:drug effects; D012737:Sex Factors; D012919:Social Behavior; D013997:Time Factors; D013998:Time Perception / Q000187:drug effects
chemical_list: D011619:Psychotropic Drugs; D018045:Receptors, Oxytocin; D010121:Oxytocin