Medial orbitofrontal cortex lesion prevents facilitatory effects of d-cycloserine during fear extinction

•We evaluate the relationship between orbitofrontal cortex and d-cycloserine in fear extinction.•Orbitofrontal cortex lesion prevents the facilitatory effect of the d-cycloserine.•Pharmacological treatments could be influenced by prefrontal activity.

Animal models of fear extinction have an important clinical relevance to pharmacological and exposure-based therapies for anxiety disorders. Lesions of prefrontal structures impair fear extinction. On the other hand, d-cycloserine is able to enhance this process. We hypothesize that the integrity of cortical structures involved in inhibitory control of emotional responses is crucial for the facilitatory effects of d-cycloserine. Here, we showed that medial orbitofrontal cortex lesion prevents d-cycloserine enhancement of fear extinction. These preliminary results suggest that effects of pharmacological treatments could be dependent on cortical activity state to promote fear memory reduction.