Methamphetamine-induced activity of matrix metalloproteinases in the striatum and prefrontal cortex of C57Bl/6J.

Abstract

Matrix metalloproteinases (MMPs) are enzymes active in the pericellular environment. Their activation and regulation are important in maintaining tissue homeostasis and synaptic physiology as they contribute to normal physiological remodeling in the brain. Their role in neuronal plasticity is of particular interest in the context of addiction as they are thought to contribute to the development of behavioral sensitization to drugs of abuse such as methamphetamine (METH). In addition, MMP upregulation is linked to long-term change in neural physiology. Methamphetamine and similar psychostimulants alter the central nervous system by increasing the amount of dopamine released in pathways in the brain through redistribution of dopamine synaptic vesicles to the cytosol. Toxic effects of METH are thought to depend on the drug’s similarity to dopamine (DA), which allows METH to enter DA axons and release DA from the synaptic vesicles. Here, we investigate the effect of high-dosage METH treatment on MMP activity in the striatum and prefrontal cortex of adult C57BI/6J mice given their role in reward, addiction, behavioral sensitization, and associated neural remodeling. A gelatin zymography method is used to measure the activity of the MMPs. MMP activity change in these areas raises an important concern about long-term effects of psychostimulant abuse to the brain. We hypothesize that increased activity of MMPs in the brain contributes to many of the synaptic changes that result in the formation of addiction pathways and may possibly lead to the “leakiness” of the blood brain barrier as a result of METH abuse. Understanding the role of increased MMP activity will further our knowledge of how drug abuse changes the brain.