Chronic Intranasal Oxytocin Causes Long-Term Impairments in Partner Preference Formation in Male Prairie Voles

Despite the accumulating evidence suggesting that the neuropeptide oxytocin (OT) plays a role in neuropsychiatric disorders characterized by social dysfunction, the influence of OT on the nonsocial aspects of learning and memory have been less investigated. To foster research in this area, we review the effects of OT on learning and memory in animal models and humans. In healthy animal models, OT improves memory consolidation and extinction, but only if given at a low dose immediately after the acquisition phase. On the contrary, OT effects in healthy humans have been inconsistent; although, in this case, OT was always given before the acquisition phase and no dose-response curves have ever been drawn up. Interestingly, a specific impairment in the reversal of learning has been found in mice devoid of OT receptors and OT has been demonstrated to enhance fear extinction in rodents. All together, these data suggest that OT plays a role in elementary forms of behavioral flexibility and adaptive responses and support its therapeutic potential in neuropsychiatric disorders characterized by cognitive inflexibility and/or impairment (autism, schizophrenia, Alzheimer's disease, Parkinson disease, stroke, posttraumatic stress disorder). Accordingly, OT has been shown to improve cognitive flexibility in OT receptordeficient mice, and scattered findings indicate that intranasal OT has positive effects on the memory of patients with schizophrenia or posttraumatic stress disorders. Further studies of the therapeutic potential of OT as an enhancer of learning and memory are warranted.

Section: Oxytocin In Learning and Memorysupporting

confidence: 53%

Section: Critical Issues and Strategiesmentioning

confidence: 99%

Learning About Oxytocin: Pharmacologic and Behavioral Issues

Chini

Leonzino

Braida

et al. 2014

“…However, relevant basic studies are rare, and those performed reveal that chronic OXT effects strongly depend on the dose and duration of application, are likely to vary between male and female subjects (65)(66)(67)(68)(69)(70)(71)(72), and are dependent upon the innate level of anxiety (65). For example, in male mice, chronic icv infusion of OXT (10 ng/hour) over 2 weeks induced a robust increase in anxiety-related behavior in two independent behavioral tests, whereas a tenfold lower dose did not alter anxiety (67).…”

Section: Chronic Effects Of Synthetic Oxt On Anxietymentioning

confidence: 99%

Oxytocin in General Anxiety and Social Fear: A Translational Approach

Neumann

Slattery

2016

381

293

The neuropeptide oxytocin (OXT) has been revealed as a profound anxiolytic and antistress factor of the brain, besides its many prosocial and reproductive effects. Therefore, there is substantial scientific and medical interest in its potential therapeutic use for the treatment of psychopathologies associated with anxiety, fear, and social dysfunctions, such as generalized anxiety disorder, posttraumatic stress disorder, and social anxiety disorder, as well as autism and schizophrenia, among others. Focusing on preclinical studies, we review the existing evidence for the regulatory capacity of OXT to fine-tune general and social anxiety-related behaviors, as well as cued and social fear conditioning from a translational perspective. The available evidence from animal and human studies substantiates the hypothesis of an imbalance of the endogenous brain OXT system in the etiology of anxiety disorders, particularly those with a social component such as social anxiety disorder. In addition, such an imbalance of the OXT system is also likely to be the consequence of chronic OXT treatment resulting in a dose-dependent reduction in OXT receptor availability and increased anxiety.

“…In male voles, a long-term developmental treatment with low doses of OXT IN resulted in a deficit in partner preference behavior (139), and in mice, chronic OXT treatment even induced an anxiogenic phenotype (140). In humans, OXT IN treatment over 10 days in elderly subjects produced no significant effects on mood or the cardiovascular indices but yielded positive changes in psychological well-being and physical functioning (141).…”

Section: Translational Implications and New Avenues For Future Researchmentioning

confidence: 99%

Dissecting the Role of Oxytocin in the Formation and Loss of Social Relationships

Hurlemann

Scheele

2016

102

Current concepts of human sociality highlight a fundamental role of the hypothalamic peptide oxytocin (OXT) in the formation and maintenance of social relationships. However, emerging evidence indicates that OXT does not invariably facilitate social bonding but also produces nonprosocial effects that may have evolved to promote offspring survival. From a mechanistic perspective, we hypothesize that OXT modulates interoceptive signals and self-referential processing, which may result in various social outcomes depending on context- and person-dependent variables such as early-life adversity. Based on this theoretical framework, we discuss translational implications for clinical trials and identify open questions for future research. Specifically, we propose that disrupted OXT signaling due to the loss of affectionate bonds may contribute to emotional disequilibrium and confer elevated risk for the onset of stress-related disorders.