A major goal of
drug abuse research is to identify and understand
drug-induced changes in brain function that are common to many or all drugs of abuse. As these may underlie
drug dependence and addiction, the purpose of the present study was to examine if different drugs of abuse effect changes in gene expression that converge in common molecular pathways. Microarray analysis was employed to assay brain gene expression in postmortem anterior prefrontal cortex (aPFC) from 42 human
cocaine, cannabis and/or
phencyclidine abuse cases and 30 control cases, which were characterized by toxicology and
drug abuse history. Common transcriptional changes were demonstrated for a majority of
drug abuse cases (N = 34), representing a number of consistently changed functional classes:
Calmodulin-related transcripts (CALM1, CALM2, CAMK2B) were decreased, while transcripts related to
cholesterol biosynthesis and trafficking (FDFT1, APOL2, SCARB1), and Golgi/endoplasmic reticulum (ER) functions (SEMA3B, GCC1) were all increased. Quantitative PCR validated decreases in
calmodulin 2 (CALM2)
mRNA and increases in
apolipoprotein L, 2 (APOL2) and
semaphorin 3B (SEMA3B)
mRNA for individual cases. A comparison between control cases with and without
cardiovascular disease and elevated body mass index indicated that these changes were not due to general cellular and metabolic stress, but appeared specific to the use of drugs. Therefore, humans who abused
cocaine, cannabis and/or
phencyclidine share a decrease in transcription of
calmodulin-related genes and increased transcription related to
lipid/
cholesterol and Golgi/ER function. These changes represent common molecular features of
drug abuse, which may underlie changes in synaptic function and plasticity that could have important ramifications for decision-making capabilities in drug abusers.