The longitudinal influence of multiple depressant use on nonfatal overdose among young people who inject drugs

or KN-93 was infused into the BLA immediately followingmemory reactivation or extinction to inhibit CaMKII. The behavioral effect of this inhibition was measured in a cue-induced reinstatement session. Next, HEK-293 cells were transfected with either wildtype or mutated (Ser331Ala) forms of CaMKII〈. Whole cell lysates were collected and specific kinase activity was assessed. Results: Intra-BLA infusions of CaMKII inhibitors decreased responding during cue-induced reinstatement relative to vehiclecontrols. Thus, CaMKII activity plays a role in drug-cue memory reconsolidation and that inhibiting this process can reduce drugseeking behavior. CaMKII inhibition after cue-extinction also resulted in decreased lever pressing during reinstatement, suggesting that CaMKII activity interfereswith the ability of cue-extinction to reduce drug-seeking behavior. Conclusions:Drug-cuememory extinction and reconsolidation maydifferentially effectCaMKII kinaseactivity throughphosphorylation at Ser331. Additionally, blocking the activity of CaMKII in the BLAcanenhanceextinctionandweaken reconsolidation tomediate drug-seeking behavior. Therefore, CaMKII activity may be required for drug-memory reconsolidation and CaMKII inhibitors may be useful adjuncts to extinction training in addiction therapy. Financial support: This research was supported by the Pennsylvania Department of Health, K01DA031745, T32NS007433, and T32DA031111.