Targeting cocaine versus heroin memories: divergent roles within ventromedial prefrontal cortex

• The vmPFC acts as an ON/OFF switch for heroin/cocaine seeking, respectively.
• Impulsive choice predicts cocaine seeking, but not heroin seeking.
• Heroin seeking may remain goal directed, whereas cocaine seeking may become habitual.
• Dopamine plays an integral role in each of these vmPFC functions.

In the search for novel treatments for addiction, most research has been propelled by the hope for a ‘magic bullet’ that would cure all forms of addiction. More recently, the field has started to appreciate the differences between psychostimulants versus opiates. Recent data suggest that the ventromedial prefrontal cortex (vmPFC) may fundamentally serve different roles in cocaine versus heroin addiction: acting as a neural OFF switch for cocaine seeking, but an ON switch for heroin seeking. We discuss the relevance of this distinction in relationship to three main functions of the vmPFC: (i) extinction memory, (ii) the suppression of impulsive behaviors, and (iii) the transition from goal-directed behaviors to habits. We highlight the importance of dopamine in modulating corticostriatal circuits for each of these functions. Finally, we conclude by discussing the implications for treatment strategies.