Metoprolol decreases retention of fear memory and facilitates long-term depression in lateral amygdala

Abstract

Posttraumatic stress disorder is a mental disorder with a known cause, yet effective behavioral and pharmacotherapies remain elusive for many afflicted patients. Propranolol is suggested to be effective as a fear-reducing agent when paired with behavioral therapy soon after trauma when psychological stress is high, possibly dampening or preventing the later development of posttraumatic stress disorder. In our previous study, we found propranolol efficaciously reduced fear retention induced by reactivation via β-adrenergic receptors in lateral amygdala. However, it is unclear which subtypes of β-adrenergic receptors dominate the function of adrenergic activation in lateral amygdala. In this study, we investigated the action of β1-adrenergic receptor antagonist-metoprolol and β2-adrenergic receptor antagonist-butoxamine on the retention of conditioned fear memory and synaptic adaptation in the lateral amygdala of rats. We found metoprolol not butoxamine attenuated the reactivation-induced strengthening of fear retention and restored the impaired long-term depression in lateral amygdala. Intra-amygdala infusion of metoprolol not butoxamine attenuated reactivation-induced enhancement of fear retention. Our results suggest that β1-adrenergic receptor antagonist-metoprolol may be more suitable for the treatment of posttraumatic stress disorder.