title: A role for matrix metalloproteinases in nicotine-induced conditioned place preference and relapse in adolescent female rats.
abstract: Reconfiguration of extracellular matrix proteins appears to be necessary for the synaptic plasticity that underlies memory consolidation. The primary candidates involved in controlling this process are a family of endopeptidases called matrix metalloproteinases (MMPs); however, the potential role of MMPs in nicotine addiction-related memories has not been adequately tested. Present results indicate transient changes in hippocampal MMP-2, -3, and -9 expression following context dependent learning of nicotine-induced conditioned place preference (CPP). Members of a CPP procedural control group also indicated similar MMP changes, suggesting that memory activation occurred in these animals as well. However, hippocampal MMP-9 expression was differentially elevated in members of the nicotine-induced CPP group on days 4 and 5 of training. Inhibition of MMPs using a broad spectrum MMP inhibitor (FN439) during nicotine-induced CPP training blocked the acquisition of CPP. Elevations in hippocampal and prefrontal cortex MMP-3 expression-but not MMP-2 and -9-accompanied reactivation of a previously learned drug related memory. Decreases in the actin regulatory cytoskeletal protein cortactin were measured in the HIP and PFC during the initial two days of acquisition of CPP; however, no changes were seen following re-exposure to the drug related environment. These results suggest that MMP-9 may be involved in facilitating the intracellular and extracellular events required for the synaptic plasticity underlying the acquisition of nicotine-induced CPP. Furthermore, MMP-3 appears to be important during re-exposure to the drug associated environment. However, rats introduced into the CPP apparatus and given injections of vehicle rather than nicotine during training also revealed a pattern of MMP expression similar to nicotine-induced CPP animals.
authors.affiliation: Department of Neurosciences, University of Toledo College of Medicine, Toledo, OH, USA.
authors.forename: Reka
authors.initials: R
authors.lastname: Natarajan
authors.affiliation: Departments of Psychology, and Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WA, USA.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Harding
authors.affiliation: Departments of Psychology, and Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WA, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Wright
keywords: FN439; MMP-3; adolescent rats; conditioned place preference; cortactin; matrix metalloproteinases; nicotine; relapse