Fter the reactivation of cocaine cue memories. Levels of pAkt and pGSK3 have been also lowered inside the prefrontal cortex. Since decreased phosphorylation of GSK3 indicates heightened enzyme activity, the impact of a selective GSK3 inhibitor, SB216763, on reconsolidation was tested. Administration of SB216763 straight away just after exposure to an environment previously paired with cocaine abrogated a previously established placepreference, suggesting that GSK3 inhibition interfered with reconsolidation of cocaine-associated reward memories. Conclusions These findings recommend that the Akt/GSK3/ mTORC1 signaling pathway within the nucleus accumbens, hippocampus, and/or prefrontal cortex is critically involved in the reconsolidation of cocaine contextual reward memory. Inhibition of GSK3 activity for the duration of memory retrieval can erase an established cocaine location preference. Keyword phrases Cocaine . Conditioned spot preference . Glycogen synthase kinase-3 . Memory . Reconsolidation . mTORC1 . Mouse . Reward . Akt . Protein kinase B . Nucleus accumbens . Hippocampus . Worry conditioningIntroduction Compulsive drug use is the hallmark of addiction, and conditioned studying plays a large role in the development of this habitual behavior (Berke and Hyman 2000). Addictive drugs which include cocaine engage molecular signaling pathways which can be ordinarily involved in associative understanding processes. Exposure to cues previously associated with cocaine availability can cause a conditioned physiological response accompanied by intense drug craving (Ehrman et al. 1992). Memories for cocaine-associated cues are hugely resistant to extinction (Miller and Marshall 2005). Conditioned responses to these cues persist throughout drug abstinence and contribute to the higher rates of relapse to cocaine use even right after prolonged periods of abstinence. Therefore, a aim of addiction treatment is usually to extinguish previously discovered associations amongst the optimistic subjective effects of cocaine and environmental cues signaling cocaine availability.Silver(I) trifluoromethanethiolate web Memories undergo a reconsolidation method right after reactivation and retrieval.1-(Difluoromethyl)-4-iodo-1H-pyrazole Chemscene Following the reactivation of cocaineassociated memories, exposure for the preceding conditioned stimulus (i.PMID:34856019 e., cue) within the absence of the unconditionedX. Shi : J. S. Miller : L. J. Harper : E. M. Unterwald (*) Division of Pharmacology as well as the Center for Substance Abuse Analysis, Temple University School of Medicine, Philadelphia, PA 19140, USA e-mail: [email protected] R. L. Poole : T. J. Gould Division of Psychology, Temple University, Philadelphia, PA, USAPsychopharmacology (2014) 231:3109?stimulus (i.e., cocaine) reactivates previously learned memories resulting in reconsolidation or strengthening on the memory (Mactutus et al. 1979; Przybyslawski and Sara 1997). Throughout the reactivation procedure, memory traces are labile and may be manipulated behaviorally or pharmacologically (Nader et al. 2000). As drug-associated cues can trigger relapse to drug-seeking behaviors, pharmacological inhibition of memory reconsolidation processes that sustain intrusive cocaine-related memories might be a useful approach to stop relapse. Although the neural circuitry of associative mastering and cue-induced drug looking for has been investigated, the molecular signaling pathways engaged within this process have not been well-described. As such, the target with the present study was to investigate the crucial intracellular signaling proteins involved inside the reconsolidation of cocaine-associated memories and to.
