Relationship between methamphetamine exposure and matrix metalloproteinase 9 expression

Abstract

Matrix metalloproteinase (MMP) 9 is up regulated following various types of insults to the brain. Recent studies have also implicated MMP9 in neural remodeling after stimulant doses of methamphetamine (METH). The involvement of MMP9 in METH‐induced neurotoxicity, however, remains unclear and was thus evaluated in the present study. Male, Swiss Webster mice were injected with stimulant or toxic doses of METH. MMP9 gene expression was up regulated in the brain within 5 min. By 24 h, MMP9 gene expression returned to control levels in the stimulant treated mice, but remained elevated in animals exposed to toxic doses of METH. The development of neurotoxicity was evidenced between 1­7 days following METH exposure as depletions in striatal dopamine levels. However, this marker of METH neurotoxicity was not accompanied by concomitant changes in striatal MMP9 gene expression. In MMP9 knock out mice, neurotoxic dosing with METH produced depletions in striatal dopamine levels that were comparable to wild type mice. Although the absence of MMP9 did not affect METH neurotoxicity, the knock out mice exhibited the expected decrease in behavioral sensitization following repeated administration of stimulant doses of METH. Together, the data suggest that changes in MMP9 expression do not affect METH‐induced neurotoxicity, and may instead be contributing to remodeling of the nervous system.