Medial prefrontal cortex activation facilitates re-extinction of fear in rats.

It has been suggested that reduced infralimbic (IL) cortical activity contributes to impairments of fear extinction. We therefore explored whether pharmacological activation of the IL would facilitate extinction under conditions it normally fails (i.e., immediate extinction). Rats received auditory fear conditioning 1 h before extinction training. Immediately prior to extinction, rats received microinfusions into the IL of the GABA(A) receptor antagonist, picrotoxin, or the NMDA receptor partial agonist, D-cycloserine. Although neither drug facilitated extinction, they both facilitated the subsequent re-extinction of fear when animals were trained in a drug-free state, suggesting that activating the IL primes behavioral extinction.