Learning About Oxytocin: Pharmacologic and Behavioral Issues

Abstract

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.

The Microbiome-Gut-Brain Axis in Health and Disease

“…IBS and depression are frequently co-morbid and the latter is associated with the presence of biomarkers of inflammation such as elevated interleukin IL-6, tumor necrosis factor alpha (TNFα) and the acute phase protein, C reactive protein (CRP) (45). Similar elevated biomarkers of inflammation have been seen in anxiety states and are known to occur as a result of stress.…”

“…Increasing attention is currently being paid to oxytocin the hypothalamic peptide which has been shown to increase sociability. The oxytocin receptor knockout mouse shows considerable deficits in social behaviour 45 and some small scale preliminary studies in humans indicate that intra-nasally administered oxytocin may positively alter social behaviour patterns. A few large clinical trials are under way to test oxytocin and related therapies for autism spectrum disorder 46 .…”

Ontogenesis of oxytocin pathways in the mammalian brain: late maturation and psychosocial disorders

“…Many reviews are exhaustive on the involvement of OT in shaping and regulating the social brain (Meyer-Lindenberg et al, 2011; Striepens et al, 2011; McCall and Singer, 2012) or in learning and memory (Chini et al, 2014). The strongest line of demonstration of the OT system in social behavior, feeding behavior and maternal care is via the study of knockout mice in which either the OT or the OTR genes are inactivated (Table 4).…”

Oxytocin Receptor <b><i>(OXTR)</i></b> Methylation and Cognition in Psychotic Disorders

“…Previous findings indicate that both general and social cognitive processes such as working memory and facial emotion recognition, respectively, are related to oxytocin function [1,2,3,4]. Within psychotic disorders such as schizophrenia, broad cognitive deficits have been well documented [5,6,7,8], and oxytocin abnormalities may contribute to these deficits.…”