Selective sub-nucleus effects of intra-amygdala oxytocin on fear extinction

Abstract

There is growing evidence that the neuropeptide oxytocin (OT) modulates fear and extinction in humans and rodents through actions in corticolimbic circuits including the central amygdala (CeA). Prior studies have, however, been limited to subjects that exhibit intact basal extinction, rather than extinction-impaired populations that could potentially therapeutically benefit from viable OT-targeting treatments. Here, we assessed the effects of pre-extinction training infusion of OT into the CeA, or basolateral amygdala (BLA), on extinction in an inbred mouse strain (S1) model of impaired extinction. We found that intra-CeA OT, at a dose of 0.01 μg, enabled extinction memory formation, as evidenced by lesser freezing as compared to vehicle-infused controls on a drug-free retrieval test. Conversely, infusion of a higher, 1.0 μg OT dose, markedly reduced freezing and increased grooming during extinction training and produced elevated freezing on drug-free retrieval. Infusion of the 0.01 μg dose into the BLA was without behavioral effects. Together, our data show that OT acts in a dose-dependent manner within the CeA to promote extinction in otherwise extinction-deficient mice. These findings provide further support for the potential utility of OT as an adjunctive treatment to extinction-based therapies for trauma and anxiety disorders.