Role of prefrontal cortex in the extinction of drug memories

It has been recognized that drug addiction engages aberrant process of learning and memory, and substantial studies have focused on developing effective treatment to erase the enduring drug memories to reduce the propensity to relapse. Extinction, a behavioral intervention exposing the individuals to the drug-associated cues repeatedly, can weaken the craving and relapse induced by drug-associated cues, but its clinic efficacy is limited. A clear understanding of the neuronal circuitry and molecular mechanism underlying extinction of drug memory will facilitate the successful use of extinction therapy in clinic. As a key component of mesolimbic system, medial prefrontal cortex (mPFC) has received particular attention largely in that PFC stands at the core of neural circuits for memory extinction and manipulating mPFC influences extinction of drug memories and subsequent relapse. Here, we review the recent advances in both animal models of drug abuse and human addicted patients toward the understanding of the mechanistic link between mPFC and drug memory, with particular emphasis on how mPFC contributes to the extinction of drug memory at levels ranging from neuronal architecture, synaptic plasticity to molecular signaling and epigenetic regulation, and discuss the clinic relevance of manipulating the extinction process of drug memory to prevent craving and relapse through enhancing mPFC function.