Influence of dorsal hippocampal lesions and MMP inhibitors on spontaneous recovery following a habituation/classical conditioning head-shake task

Abstract

The present investigation combined a classical conditioning paradigm with a head-shake response (HSR) habituation task in order to evaluate the importance of dorsal hippocampal neural plasticity to spontaneous recovery. In the first experiment animals exhibited rapid HSR habituation (air stimulus to the ear) and an 85% level of spontaneous recovery following a 24 h inter-session interval. The addition of a brief tone prior to the air stimulus produced a similar pattern of habituation during the first session, but the level of spontaneous recovery was reduced (44%) during Session II. In a second experiment dorsal hippocampal lesioned rats placed on this tone/HSR paradigm responded with an 87% level of spontaneous recovery during Session II; while neocortex lesioned control rats indicated significantly reduced levels of spontaneous recovery (55%). In a third experiment bilateral injections of a general MMP inhibitor, FN-439, into the dorsal hippocampus resulted in high levels of spontaneous recovery (81%); while control rats injected with artificial cerebrospinal fluid displayed a significant attenuation of spontaneous recovery (45%). Finally, animals bilaterally injected with a specific MMP-3 inhibitor into the dorsal hippocampus indicated very similar results to those obtained following FN-439 injection. These findings indicate that animals prepared with dorsal hippocampal lesions, or injections with an MMP inhibitor, revealed an impaired association between the tone and air stimulus thus maximum spontaneous recovery was present 24 h later. Thus, it appears that the dorsal hippocampus influences habituation by conserving responses and reducing spontaneous recovery when a temporally contingent signaling cue is present.