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Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR) kinase, has attracted interest as a possible prophylactic for post-traumatic stress disorder (PTSD)-associated fear memories. We report here that although rapamycin (40 mg/kg, i.p.) disrupted the consolidation and reconsolidation of fear-potentiated startle paradigm to a shock-paired context, it did not disrupt startle increases to a 4-sec odor cue, even though post-training increases in amygdala mTOR activity were prevented by rapamycin (also 40 mg/kg, i.p.). Thus, while rapamycin may prove useful in retarding the development of some PTSD-associated memories, its relative ineffectiveness against cued fear memories may limit its clinical usefulness.

Differing effects of systemically administered rapamycin on consolidation and reconsolidation of context vs. cued fear memories