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Reactivation of cocaine-associated memories plays a critical role in reinstating the cocaine-seeking behavior and causing relapse. Cocaine-induced conditioned place preference (CPP) was used as a behavioral paradigm indicative of cocaine-associated memory and repeated cocaine-free preference tests served as a behavioral procedure to retrieve such a memory in this study. Since D-cycloserine was reported to eradicate drug-associated memories, two other N-methyl-D-aspartate (NMDA) receptor agonists were assessed for their efficacy on facilitating the extinction of cocaine-induced CPP. Although D-cycloserine (30 mg/kg) abolished cocaine (10 mg/kg)-induced CPP, sarcosine (300 and 600 mg/kg) and D-serine (600 mg/kg) diminished the expression of such a cocaine memory. Sarcosine (600 mg/kg) and D-serine (600 mg/kg) did not affect the storage of this cocaine memory. It was of interest to note that D-cycloserine facilitated the extinction of cocaine-induced CPP in a fast and early-onset manner, while sarcosine and D-serine decreased cocaine-induced CPP expression in a delay-onset manner. D-cycloserine (30 mg/kg), D-serine (600 mg/kg) and sarcosine (600 mg/kg) did not affect the consolidation of cocaine (5 mg/kg)-induced CPP. Finally, sarcosine (at 600 mg/kg/day for 3 consecutive days) and D-serine (at 600 mg/kg/day for 3 consecutive days) did not produce observable aversive effect associated with their administration in a conditioned place aversion paradigm. Likewise, a similar dosing regimen of sarcosine or D-serine did not cause evident activity-impairing effect. In addition to D-cycloserine treatment, our results indicate that long-term treatment with D-serine and sarcosine may afford a therapeutic advance in suppressing the expression of cocaine-associated memory. [ABSTRACT FROM PUBLISHER]

This study was undertaken to test whether de novo protein synthesis in the basolateral (BLA) and central (CeA) nucleus of amygdala was required for reconsolidation of emotion-related memories. Mice were trained to sequentially acquire both cocaine-induced conditioned place preference (CPP) and step through passive avoidance (PA) memories. Immediately following PA retrieval, intra-BLA anisomycin infusion was found to decrease subsequent PA performance in retests. Immediately following PA retrieval, intra-CeA anisomycin infusion did not acutely affect PA performance but decreased such a PA memory 5 days later. Given PA retrieval procedure was omitted, intra-BLA and intra-CeA anisomycin infusion did not affect PA memory. Likewise, intra-BLA anisomycin infusion immediately following cocaine-induced CPP retrieval was found to decrease cocaine-induced CPP magnitude in early and late retests. Immediately after cocaine-induced CPP retrieval, intra-CeA anisomycin infusion did not acutely affect cocaine-induced CPP but decreased this memory 5 days later. Given the cocaine-induced CPP retrieval procedure was omitted, intra-BLA and intra-CeA anisomycin infusion did not affect cocaine-induced CPP in subsequent retests. These results, taken together, imply that de novo protein synthesis in amygdala plays an important role in modulating reconsolidation of emotion-related memory. More importantly, de novo protein synthesis in the BLA is essential for early phase reconsolidation of retrieved emotion-related memories. Protein synthesis in the CeA is required for late phase reconsolidation of retrieved emotion-related memories.