Memory reconsolidation of cocaine-associated context requires nitric oxide signaling.

Recent studies suggest that long-term memory (LTM) is labile because retrieval of such memories may undergo a reconsolidation process which is vulnerable to disruption. Nitric oxide (NO) is a retrograde messenger involved in synaptic plasticity and LTM. In the present study the role of NO in reconsolidation of LTM of cocaine-associate context was investigated in wild type (WT) and neuronal nitric oxide synthase (nNOS) deficient mice (knockout; KO). LTM of cocaine-associated context was established in both WT and nNOS KO mice by conditioned place preference learning. Subsequently, the retrieval of place preference in WT mice was challenged by either saline or the selective nNOS inhibitor 7-nitroindazole, and retrieval of place preference in KO mice was challenged by either saline or the NO-donor molsidomine. Results suggest that in the absence of nNOS activity, particularly during the reconsolidation phase, LTM of cocaine-associated context is extinguished.