Cocaine use disorder alters gene networks of neuroinflammation and neurotransmission in humans
Individuals with cocaine use disorder exhibit gene expression changes in two brain regions: the nucleus accumbens, a region associated with reward, and the caudate nucleus, a region mediating habit formation, according to research conducted at the Icahn School of Medicine at Mount Sinai and published February 10 in Science Advances.
These changes, which contribute importantly to the persistent behavioral abnormalities seen in addiction to drugs, occur because cocaine use sets off a series of chemical reactions that lead to increases in the amount of messenger RNA being produced from some of the affected genes in these two brain regions, whereas the activity of other genes decreases. Changes in the amount of messenger RNA produced—a process also known as “expression” of the underlying genes—lead to changes in the amount of proteins that are produced and that subsequently carry out chemical reactions in the brain. The research team found a significant overlap between the RNAs expressed in these two brain regions, suggesting that these molecular changes may be key to the development and maintenance of cocaine use disorder.
To address the knowledge gap, the research team performed RNA sequencing in both the nucleus accumbens and caudate nucleus from the postmortem brain tissue of persons with cocaine use disorder and matched controls. Using the largest and most diverse cohort examined to date, they found that neuroinflammatory processes are suppressed and that synaptic transmembrane transporters and ionotropic receptors – proteins that control how nerve cells communicate with one another in the brain—are enriched in the striatum of people with cocaine use disorder.
Cocaine increases the amount of the neurotransmitter dopamine at synapses, or junctions between two brain cells where electrical signals are converted into chemical signals. By doing so, the research team found, cocaine sets off a cascade of events that activate a chemical messenger in the brain called cyclic AMP, which then triggers changes in gene expression.
