Brain Oxytocin in Social Fear Conditioning and Its Extinction: Involvement of the Lateral Septum

Abstract

Central oxytocin (OXT) has anxiolytic and pro-social properties both in humans and rodents, and has been proposed as a therapeutic option for anxiety and social dysfunctions. Here, we utilized a mouse model of social fear conditioning (SFC) to study the effects of OXT on social fear, and to determine whether SFC causes alterations in central OXT receptor (OXTR) binding and local OXT release. Central infusion of OXT, but not arginine vasopressin, prior to social fear extinction training completely abolished social fear expression in an OXTR-mediated fashion without affecting general anxiety or locomotion. SFC caused increased OXTR binding in the dorso-lateral septum (DLS), central amygdala, dentate gyrus, and cornu ammunis 1, which normalized after social fear extinction, suggesting that these areas form part of a brain network involved in the development and neural support of social fear. Microdialysis revealed that the increase in OXT release observed in unconditioned mice within the DLS during social fear extinction training was attenuated in conditioned mice. Consequently, increasing the availability of local OXT by infusion of OXT into the DLS reversed social fear. Thus, alterations in the brain OXT system, including altered OXTR binding and OXT release within the DLS, play an important role in SFC and social fear extinction. Thus, we suggest that the OXT system is adversely affected in disorders associated with social fear, such as social anxiety disorder and reinstalling an appropriate balance of the OXT system may alleviate some of the symptoms.

Oxytocin Facilitates Pavlovian Fear Learning in Males

“…In our previous work, it was found that a single-dose administration of OXT potentiates episodic encoding of aversive events as well as the extinction of conditioned fear (Eckstein et al, 2014b) by amplifying activity in extra-amygdalar regions, including insular cortex, precuneus, and dorsomedial prefrontal cortex. In the present study, OXT enhanced pMCC responses to social stimuli during fear conditioning, which is consistent with findings in mice suggesting that OXT specifically facilitates social fear conditioning (Zoicas et al, 2014). Taken together with previous research (Eckstein et al, 2014a;Striepens et al, 2012), this study presents a model of OXT as an enhancer of adaptation in social contexts.…”

Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder

“…Notably, the vmPFC is important in extinction learning, the underlying mechanism of exposure therapy (Rothbaum and Davis, 2003) and the treatment of choice for PTSD (Foa et al, 2009). Previous animal (Zoicas et al, 2014) and human studies (eg, Eckstein et al, 2014) have shown that OT administration enhanced extinction learning (but see (Acheson et al, 2015). In healthy individuals, OT administration increased prefrontal involvement during the early phase of fear extinction and attenuated general amygdala responsivity (Eckstein et al, 2014).…”

Methamphetamine abstinence induces changes in μ-opioid receptor, oxytocin and CRF systems: Association with an anxiogenic phenotype

“…In fact, we have previously shown that decreased OT content in the brain was concomitant with an increase in the OTR in the lateral septum (Zanos et al, 2014). In addition, Zoicas et al, (2014) have demonstrated that social fear conditioning was associated with an increase in OTR binding in the septum of rodents, whereas i.c.v.…”