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

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.