Retrieval of memory for fear-motivated training initiates extinction requiring protein synthesis in the rat hippocampus

Evidence that protein synthesis inhibitors induce amnesia in a variety of s pecies and learning paradigms indicates that the consolidation of newly acq uired information into stable memories requires the synthesis of new protei ns. Because extinction of a response also requires acquisition of new infor mation, extinction, like original learning, would be expected to require pr otein synthesis. The present experiments examined the involvement of protei n synthesis in the hippocampus in the extinction of a learned fear-based re sponse known to involve the hippocampus. Rats were trained in a one-trial i nhibitory avoidance task in which they received footshock after stepping fr om a small platform to a grid floor. They were then given daily retention t ests without footshock. The inhibitory response (e.g., remaining on the pla tform) gradually extinguished with repeated testing over several days. Foot shock administered in a different context, instead of a retention test, pre vented the extinction. Infusions of the protein synthesis inhibitor anisomy cin (80 mug) into the CA1 region of the hippocampus (bilaterally) 10 min be fore inhibitory avoidance training impaired retention on all subsequent tes ts. Anisomycin infused into the hippocampus immediately after the 1st reten tion test blocked extinction of the response. Infusions administered before the 1st retention test induced a temporary (i.e., 1 day) reduction in rete ntion performance and blocked subsequent extinction. These findings are con sistent with other evidence that anisomycin blocks both the consolidation o f original learning and extinction.