Brexpiprazole blocks post-traumatic stress disorder-like memory while promoting normal fear memory.

Area of Science:

• Neuroscience
• Pharmacology
• Psychiatry

Background:

• Post-traumatic stress disorder (PTSD) is characterized by paradoxical memory alterations: hypermnesia for trauma cues and amnesia for context.
• Current pharmacological treatments for PTSD are limited due to a lack of suitable animal models for its memory deficits.

Purpose of the Study:

• To investigate the efficacy of brexpiprazole in a novel mouse model that replicates the dual memory components of PTSD.
• To determine if brexpiprazole can prevent the expression of PTSD-like memory and normalize associated neural network activity.

Main Methods:

• Utilized a mouse model of PTSD involving fear conditioning and corticosterone injection to induce specific memory alterations.
• Administered brexpiprazole acutely (0.3 mg/kg) post-trauma and assessed memory recall and hippocampal-amygdalar network activation (C-Fos expression).
• Compared brexpiprazole's effects to diazepam, prazosin, and escitalopram on fear memory and contextual memory.

Main Results:

• Brexpiprazole blocked maladaptive fear memory for trauma cues and enhanced memory for the traumatic context, outperforming other tested drugs.
• These beneficial effects were maintained one week after treatment and did not impair normal fear memory.
• Brexpiprazole normalized hippocampal-amygdalar network activation patterns associated with PTSD-like memory.

Conclusions:

• Brexpiprazole effectively promotes a switch from PTSD-like memory to normal fear memory in a preclinical model.
• The drug normalizes key neural circuit dysfunctions underlying PTSD-like memory.
• Brexpiprazole shows promise as a novel pharmacological treatment for PTSD by targeting traumatic memory normalization.