Cocaine epigenetically manipulates the brain

CHRISTMAS GUILLON

Dopamine, a neurotransmitter, is involved as an epigenetic agent in the mechanisms of relapse after withdrawal from cocaine.

Dopamine is a neurotransmitter notably involved in the reward circuits. A new study has highlighted its epigenetic role in neurons.

The persistence of the risk of relapse after withdrawal from cocaine is still very poorly understood. Scientists have long felt that rewiring of the brain’s reward circuits was at stake. This phenomenon could involve epigenetic manipulation of certain neurons by cocaine, that is to say a modification not of the sequence of their DNA. , but how this genetic code is expressed. Ashley Lepack and her colleagues at Mount Sinai Hospital in New York and State University of New York at Buffalo have just shown in rats that cocaine self-administration, followed by a period of abstinence leads to epigenetic changes inside the neurons that produce dopamine, located in the ventral tegmental area of ​​the brain (VTA).

Cocaine is known to increase the neurotransmission of dopamine between VTA and brain areas of the reward. This drug blocks dopamine reuptake pumps on the surface of neurons. The neurotransmitter accumulates in the extracellular medium (in the synapse) and is less present in neurons. It is this excess dopamine in the synapse that amplifies its effect and produces the euphoria associated with cocaine use.

During withdrawal, dopamine would play another completely unexpected role. This time inside neurons, it would bind, more than in non-cocaine users, on certain histones, proteins around which DNA is wound and which allow it to compact inside core. Modulation of compaction, as well as the ability of histones to interact with other nuclear elements, affects gene expression. By binding to histones, certain molecules act on the coiling of DNA and the recruitment of transcription factors: this is called epigenetic modification.

Leave a Reply

Your email address will not be published. Required fields are marked *