It is difficult to diminish long-term traumatic memories with behavioural therapy, making it challenging to treat anxiety disorders. This study showed that administration of a histone deacetylase 2 (HDAC2) inhibitor to mice during a specific phase of traumatic memory recall — known as memory reconsolidation — rendered month-old memories susceptible to attenuation by behavioural therapy. The HDAC2 inhibitor epigenetically primed the expression of genes related to neuronal plasticity and increased the synaptic and structural plasticity of neurons. So, HDAC2 inhibitors could be used with behavioural therapy to eliminate long-term traumatic memories.