Role of matrix metalloproteinases in the acquisition and reconsolidation of cocaine-induced conditioned place preference.

Full Abstract

Persistent drug seeking/taking behavior involves the consolidation of memory. With each drug use, the memory may be reactivated and reconsolidated to maintain the original memory. During reactivation, the memory may become labile and susceptible to disruption; thus, molecules involved in plasticity should influence acquisition and/or reconsolidation. Recently, matrix metalloproteinases (MMPs) have been shown to influence neuronal plasticity, presumably by their regulation of extracellular matrix (ECM) molecules involved in synaptic reorganization during learning. We hypothesized that inhibition of MMP activity would impair the acquisition and/or reconsolidation of cocaine-conditioned place preference (CPP) in rats. Intracerebral ventricular (i.c.v.) microinjection of a broad spectrum MMP inhibitor, FN-439, prior to cocaine training suppressed acquisition of CPP and attenuated cocaine-primed reinstatement in extinguished animals. In a separate experiment, the cocaine memory was reactivated on two consecutive days with a cocaine priming injection. On these two days, artificial cerebral spinal fluid (aCSF) or FN-439 was administered either 30 min prior to or 1 min after cocaine-primed reinstatement sessions. Infusion of FN-439 partially impaired retrieval of the cocaine-associated context when given 30 min prior to cocaine. In both groups, however, FN-439 suppressed reinstatement compared with controls on the third consecutive test for cocaine-primed reinstatement, when no FN-439 was given. Control experiments demonstrated that two injections of FN-439 + cocaine given in the home cage, or of FN-439 + saline priming injections in the CPP chambers did not disrupt subsequent cocaine-primed reinstatement. These results show for the first time that (1) MMPs play a critical role in acquisition and reconsolidation of cocaine-induced CPP, and (2) rats demonstrate apparent disruption of reconsolidation by an MMP inhibitor after extinction and while they are under the influence of cocaine during reinstatement.

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Author information

Author/s: Brown, Travis E (TE); Forquer, Melissa R (MR); Cocking, Davelle L (DL); Jansen, Heiko T (HT); Harding, Joseph W (JW); Sorg, Barbara A (BA);

Affiliation: Alcohol and Drug Abuse Research Program and Program in Neuroscience, Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington 99164-6520, USA.

Grants: DA 14915 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Learning & memory (Cold Spring Harbor, N.Y.) (Learn Mem), published in United States. (Language: eng)

Reference: 2007-Mar; vol 14 (issue 3) : pp 214-23

Dates: Created 2007/06/19; Completed 2007/07/03; Revised 2008/11/20;

PMID: 17353546, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Cocaine - administration & dosage; pharmacology
Conditioning, Operant - drug effects; physiology
Drug Administration Schedule
Extinction, Psychological - drug effects
Hippocampus - enzymology
Hydroxamic Acids - administration & dosage; pharmacology

Injections, Intraventricular
Male
Matrix Metalloproteinases - antagonists & inhibitors; physiology
Oligopeptides - administration & dosage; pharmacology
Rats
Rats, Sprague-Dawley
Reinforcement (Psychology)

Associated Chemicals: 4-aminobenzoyl-glycyl-prolyl-leucyl-alanine hydroxamic acid (0) ; Hydroxamic Acids (0) ; Oligopeptides (0) ; Cocaine (50-36-2) ; Matrix Metalloproteinases (EC 3.4.24.-)

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