P.1.008 Recruitment of the mTOR complex 1 by 5-HT6 receptors: potential role in the cognitive deficits of schizophrenia

Abstract

Oxytocin (OT) has received substantial interest in recent years due to its pro-social and anxiolytic properties. In this study we investigated whether central OT administration facilitates the extinction of social and cued fear in rodents. Social fear was induced by social fear conditioning [1], while cued fear was induced by cued fear conditioning [2]. Social and cued fear extinction were performed 24 h later in a novel environment. OT was administered intracerebroventricularly 10min before the extinction procedure. While central OT completely blocked social fear expression, reversing thereby social fear, it impaired cued fear extinction. Both the facilitatory effect on social fear extinction and the impairing effect on cued fear extinction were mediated by the OT receptors, as administration of an OT receptor antagonist prior to OT blocked the observed effects. At the doses used in the fear extinction studies OT did not alter home cage locomotion, indicating that the observed effects were not a result of impaired locomotion. Taken together, this data suggests that OT has a differential effect on fear extinction in social versus nonsocial contexts, and draws attention to the implications of using OT as a potential adjunct drug in combination with behavioral therapy for psychiatric disorders. Therefore, OT might represent a therapeutically-promising approach in patients with deficits in social functioning, such as social anxiety disorder and autism spectrum disorders. However, in patients where the fear does not involve a social component, such as post-traumatic stress disorder, OT may delay fear extinction.