Cocaine addiction is a chronic, recurrent brain condition with no recognized drug therapies at the moment. A new study published today reveals what happens in the brain when someone takes cocaine.
The regulation of gene expression in the brain’s reward and motivation centers is believed to be crucial in the persistent behavioral changes associated with addiction, but there is limited understanding of the adverse gene activity caused by chronic cocaine use in these circuits in humans and the mechanisms behind Cocaine Use Disorder.
A new study conducted by researchers at the Icahn School of Medicine at Mount Sinai and published in Science Advances today found that people with cocaine use disorder have changes in gene expression in two parts of the brain: the nucleus accumbens, which is linked to reward, and the caudate nucleus, which helps form habits.
The use of cocaine sets off a chain of chemical reactions that increase the amount of messenger RNA made by some of the affected genes in these two brain regions while decreasing the activity of other genes. These changes are a big reason why drug addiction causes people to behave in strange ways for a long time.
A change in the quantity of messenger RNA generated, often known as the “expression” of the underlying genes, causes a corresponding change in the number of proteins produced, which in turn alters the amount of proteins that carry out chemical processes in the brain.
The research team found that there was a lot of overlap between the RNAs that were expressed in these two brain regions. This suggests that these molecular changes may be key to how cocaine use disorder develops and stays in place.
Cocaine addiction is a chronic, recurrent brain condition with no recognized drug therapies at the moment.
There is currently little known about the maladaptive gene activity that chronic cocaine use causes in these circuits in humans and that underlies cocaine use disorder, despite the fact that it is hypothesized that regulation of gene expression in the brain’s reward and motivational centers plays a critical role in the persistent behavioral changes that define addiction.
The study team used postmortem brain tissue from individuals with cocaine use disorder and matched controls to conduct RNA sequencing in the nucleus accumbens and caudate nucleus in an effort to close the knowledge gap.
Using the largest and most diverse group of people studied to date, they found that neuroinflammatory processes are slowed down and that there are more synaptic transmembrane transporters and ionotropic receptors in the striatum of people with cocaine use disorder. These are proteins that control how nerve cells in the brain talk to each other.
Cocaine raises levels of the neurotransmitter dopamine at synapses, the points where electrical messages are turned into chemical ones, between brain cells.
The study’s authors discovered that when cocaine enters the brain, it activates a chemical messenger called cyclic AMP, which in turn causes changes in gene expression.
According to Philipp Mews, PhD, Instructor of Neuroscience at Icahn Mount Sinai and co-author of the paper, the study not only provides novel understanding of the molecular alterations brought about by cocaine use but also reveals that individuals with Cocaine Use Disorder exhibit gene dysregulation linked to schizophrenia and major depressive disorder, pointing to the possibility of common underlying gene regulatory and neural circuit systems for these disorders.
According to the authors, the transcriptional abnormalities, particularly the suppressed neuroinflammatory responses in the nucleus accumbens of those with Cocaine Use Disorder, are in stark contrast to the proinflammatory cascade responses caused by Opioid Use Disorder. This observation of distinct molecular changes brought about by each substance use disorder has significant potential for the creation of specifically tailored and effective treatments for Cocaine Use Disorder.
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