Differential effects of dorsal hippocampal inactivation on expression of recent and remote drug and fear memory

Abstract

Drugs of abuse generate strong drug-context associations, which can evoke powerful drug cravings that are linked to reinstatement in animal models and to relapse in humans. Work in learning and memory has demonstrated that contextual memories become more distributed over time, shifting from dependence on the hippocampus for retrieval to dependence on cortical structures. Implications for such changes in the structure of memory retrieval to addiction are unknown. Thus, to determine if the passage of time alters the substrates of conditioned place preference (CPP) memory retrieval, we investigated the effects of inactivation of the dorsal hippocampus (DH) with the GABA-A receptor agonist muscimol on expression of recent or remote CPP. We compared these effects with the same manipulation on expression of contextual fear conditioning. DH inactivation produced similar deficits in expression of both recent and remote CPP, but blocked expression of recent but not remote contextual fear memory. We describe the implications of these findings for mechanisms underlying long-term storage of contextual information.

Keywords: Cocaine; Conditioned place preference; Fear conditioning; Muscimol; Systems consolidation.