Structural and metabolic brain changes in the striatum associated with methamphetamine abuse

          Methamphetamine has proven to be a highly toxic substance to neurons in rodents, primates, and humans. Clinical observations indicate that chronic use can cause persistent neurotoxicity, paranoia, and psychosis. This study reports that meth abuse causes serious changes in brain function involving the “dopaminergic and serotonergic systems , glucose metabolism, neurometabolite levels and even gross structural abnormalities.” Neuroimaging studies in humans shows these changes occurring especially in the basal ganglia (striata), which include “the putamen and globus pallidus dorsally, and the nucleus accumbens ventrally.” This region of the brain is very dense in dopaminergic neurons. Because methamphetamine acts primarily on the dopamine system, it is logical that these regions would receive the most damage. Although many of these neuronal changes do not recover after abstinence, there are some changes that have proven to reduce in severity over time following abstinence from meth use.

            According to MRI studies documented in this report, the basal ganglia appeared to be enlarged in volume in chronic meth users who were then abstinent for 3-4 months during the study. Other areas of the brain such as the thalamus, cerebellum, corpus callosum, and midbrain appeared to be of normal volume. During early abstinence from meth use (<4 months), there appeared to be an increase in white matter in the basal ganglia, which then decreased to normal levels after 20 months of abstinence. According to the report, “The early enlargement of these brain structures suggests methamphetamine-induced inflammation or reactive gliosis, which may normalize with longer abstinence from methamphetamine use.”

            Here, the report suggests the striatal enlargement may be due to increased water content within the neurons associated with the brain’s inflammatory response. Glial cell activation, which is a part of the brain’s immune response has been documented to be affected by meth use. For example, the article states, “In vitro studies demonstrated that methamphetamine contributes to central nervous system (CNS) inflammation by stimulating increased release and/or activation of matrix degrading proteinases, which would lead to breakdown of the blood–brain barrier and the influx of inflammatory cytokines, chemokines and macrophages into the brain.” In vivo studies of methamphetamine administration to rodents and non human primates also show that glial cells and other mediators associated with the inflammatory response are indeed activated. This cell damage in the blood brain barrier and the brain itself is most likely due to an unnatural increase in metabolic demand throughout this region of the brain.

http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.2006.01782.x/full