Long-term memory: disruption by inhibitors of protein synthesis and cytoplasmic flow

Colchicine (60 micrograms/kg), an inhibitor of axoplasmic transport, administered subcutaneously to mice had no detectable effect on retention when given shortly after active avoidance training, nor did a pretraining injection of anisomycin (ANI) have an amnesic effect. However, when ANI was administered shortly prior to training and colchicine was administered after training, retention performance was impaired. The amnesic effect was dependent on the time at which colchicine was administered. The amnesic effect was also obtained when ANI was combined with either vinblastine (6 micrograms/kg) or podophyllotoxin (3 micrograms/kg), drugs that inhibit axoplasmic transport. Intracerebral injections of colchicine (60 ng to 60 pg) caused amnesia in subjects pretreated with ANI, but not in subjects pretreated with saline. Lumicolchicine, an isomer of colchicine, which has similar central nervous system effects but has a low binding affinity for microtubule protein, did not impair retention in ANI pretreated mice. It is suggested that axonal transport of recently synthesized protein is required for long-term memory storage.