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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.

SUBMITTER: Huang H

PROVIDER: S-EPMC3957104 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Chronic and acute intranasal oxytocin produce divergent social effects in mice.

Huang Huiping H Michetti Caterina C Busnelli Marta M Managò Francesca F Sannino Sara S Scheggia Diego D Giancardo Luca L Sona Diego D Murino Vittorio V Chini Bice B Scattoni Maria Luisa ML Papaleo Francesco F

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20131104 5

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 mig ...[more]

PMID: 24190025

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Project description:In socially monogamous titi monkeys, involuntary separation from a pair mate can produce behavioral distress and increased cortisol production. The neuropeptide oxytocin (OXT) is thought to play an important role in the separation response of pair-bonded species. Previous studies from our lab have shown that chronic intranasal oxytocin (IN OXT) during development can have long-term effects on adult social behavior. In the current study, we examined the chronic and acute effects of IN OXT or Saline (SAL) on the subjects' response to a brief separation from their pair mates. Subjects with a history of chronic IN OXT or SAL treatment during development received a single dose of OXT or SAL as adults 30 min before being separated from their pair mate. Chronic treatment consisted of a daily dose of IN OXT (0.8 IU/kg) or SAL (control) from 12 to 18 months of age. Subjects (N = 29) were introduced to a pair mate at 30 months of age. After the pairs had cohabitated for 5 months, pairs underwent two "Brief Separation" (OXT and SAL) and two "Non-Separation" (OXT and SAL) test sessions. Vocalizations and locomotion were measured as behavioral indices of agitation or distress during the Brief Separation and Non-Separation periods (30 min each). We collected blood samples after the Brief Separation and Non-Separation periods to measure cortisol levels. Our results showed subjects treated with chronic OXT had a reduction in long call and peep vocalizations compared to subjects treated with chronic SAL. Subjects treated with chronic SAL and acute OXT produced more peeps and long calls compared to animals treated with acute SAL; however, patterns in this response depended on sex. Cortisol and locomotion were significantly higher during the Brief Separation period compared to the Non-Separation period; however, we did not find any treatment or sex effects. We conclude that chronic IN OXT given during development blunts the separation response, while acute OXT in chronic SAL subjects had sexually dimorphic effects, which could reflect increased partner seeking behaviors in males and increased anxiety in females.

Project description:Recent studies support the hypothesis that the adverse effects of early-life adversity and transgenerational stress on neural plasticity and behavior are mediated by inflammation. The objective of the present study was to investigate the immune and behavioral programing effects of intranasal (IN) vasopressin (AVP) and oxytocin (OXT) treatment of chronic social stress (CSS)-exposed F1 dams on F2 juvenile female offspring. It was hypothesized that maternal AVP and OXT treatment would have preventative effects on social stress-induced deficits in offspring anxiety and social behavior and that these effects would be associated with changes in interferon-? (IFN?). Control and CSS-exposed F1 dams were administered IN saline, AVP, or OXT during lactation and the F2 juvenile female offspring were assessed for basal plasma IFN? and perseverative, anxiety, and social behavior. CSS F2 female juvenile offspring had elevated IFN? levels and exhibited increased repetitive/perseverative and anxiety behaviors and deficits in social behavior. These effects were modulated by AVP and OXT in a context- and behavior-dependent manner, with OXT exhibiting preventative effects on repetitive and anxiety behaviors and AVP possessing preventative effects on social behavior deficits and anxiety. Basal IFN? levels were elevated in the F2 offspring of OXT-treated F1 dams, but IFN? was not correlated with the behavioral effects. These results support the hypothesis that maternal AVP and OXT treatment have context- and behavior-specific effects on peripheral IFN? levels and perseverative, anxiety, and social behaviors in the female offspring of early-life social stress-exposed dams. Both maternal AVP and OXT are effective at preventing social stress-induced increases in self-directed measures of anxiety, and AVP is particularly effective at preventing impairments in overall social contact. OXT is specifically effective at preventing repetitive/perseverative behaviors, yet is ineffective at preventing deficits in overall social behavior.

Project description:Interactions between social experiences at different stages of development (e.g., with parents as juveniles and peers as subadults) can profoundly shape the expression of social behavior. Rarely are the influences of more than one stage of developmental sensitivity to social environment investigated simultaneously. Furthermore, oxytocin (OT) has an extraordinary effect on a breadth of social behaviors, activationally or organizationally. The use of intranasal OT (IN-OT) has become increasingly common therapeutically in humans and scientifically in non-human experiments, however very little attention has been paid to the potential developmental consequences on social behavior that might result. We investigated the effects of early-life social environments and the impact of chronic IN-OT on social behavior at different stages of development in male prairie voles (Microtus ochrogaster). We raised animals under two conditions: "socially enriched" (in which they were biparentally reared and then weaned into group housing as subadults), or "socially limited" (in which they were reared by a single-mother, and that were then weaned into social isolation). Males raised under each condition were either administered daily doses of IN-OT or a saline control for 21 days from postnatal day (PND) 21-42. During this time, we assessed the prosocial behavior subjects demonstrated by evaluating juvenile affiliation (as subadults), alloparental care (as adults no longer being exposed to IN-OT), and partner preference tests to assess tendencies to form adult monogamous pairbonds. We found that "socially limited" males, exhibited increased social contact in juvenile affiliation tests at PND 35 and 42. These males were also more likely to form a partner preference than "socially enriched" males and formed stronger partner preferences overall. IN-OT did not alter these behavioral effects. We also found that "socially limited" males exhibited a distinct response to chronic IN-OT treatment. When compared to all other treatment groups, "socially limited" males that received IN-OT exhibited a greater amount of huddling behavior in the alloparental care test. This effect was, in part, explained by an absence of attack behavior, found only in these males. This study contributes to understanding the complex interactions between the developmental social environment, oxytocin, and social behavior.

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Chronic and acute intranasal oxytocin produce divergent social effects in mice.

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Chronic and acute intranasal oxytocin produce divergent social effects in mice.

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