An exploratory analysis of methamphetamine-induced break down of the blood brain barrier in C57Bl/6J.

Abstract

The blood brain barrier (BBB) is a complex membranous system of brain capillary endothelial cells, pericytes, astrocytes, and nerve endings that play a central role in maintaining the homeostasis of the central nervous system by blocking the movement of all molecules except those relatively small molecules can cross cell membranes by means of lipid solubility (oxygen, carbon dioxide, ethanol, and steroid hormones) and those transported by specific transport systems. 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). 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. 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 BBB as a result of METH abuse. Here, we investigate the effect of high-dosage METH treatment BBB breakdown in the striatum and prefrontal cortex of adult C57BI/6J mice given their role in reward, addiction, behavioral sensitization, and associated neural remodeling.