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Perspectives on Neuroscience and Behavior

Memory has a very dynamic neurobiological basis, and it has been found that when a previously consolidated memory is reactivated it enters a labile state where it can be modified prior to being reconsolidated. Now it has been shown in rats exposed to cocaine, morphine, or heroine that when a drug memory is reactivated 10 minutes or 60 minutes prior to extinction training this reduces drug-induced reinstatement, conditioned drug effects, and spontaneous reemergence of drug-related behavior that occurs with the passage of time. This was not seen when the drug memory was activated 6 hours prior to extinction training, indicating a “reconsolidation window” during which the effect can occur. In rats trained to self-administer cocaine, memory reactivation 10 minutes before extinction training increased protein levels of protein kinase M zeta (PKM zeta) in infralimbic cortex and decreased it in basolateral amygala, suggesting a mechanistic role in the observed behavioral effects of this constitutively active protein that mediates maintenance of appetitive and aversive memories. In three groups (22 in each group) of male detoxified abstinent heroin addicts the group that retrieved drug-associated memories 10 minutes prior to a 45-minute extinction session on two successive days had reduced cueinduced heroin craving assessed 1, 30, and 180 days later compared with the group that viewed a neutral video 10 minutes before the extinction session or the group that retrieved drugassociated memories 6 hours before the extinction session during the same 2-day period (Xue and others 2012). These findings demonstrate that memory retrieval prior to extinction training could be an important method to reduce drug craving of addicted individuals during abstinence; however, it remains to be demonstrated that this effect is robust enough to reduce relapse to drug taking when addicts return to their previous drug taking environments. at the mechanistic level, memory retrieval prior to extinction training could act by improving new learning during extinction or act by disrupting reconsolidation of memory. The increase in PKM zeta in infralimbic cortex (new learning) and decrease in basolateral amygala (disruption of reconsolidation) following memory retrieval and extinction suggests that it possibly does both. Taken together, these important new findings suggest that memory retrieval prior to extinction could improve outcomes when extinction-based methods are used to treat a variety of conditions such as drug addiction, posttraumatic stress disorder, and other anxiety disorders.