Cocaine addiction may often lead to deadly consequences. Neuroscientists from the Rockefeller University share that MicroRNAs associated to cancer, heart disease and mental disorders like schizophrenia are also involved in cocaine addiction. It was ascertained that a protein which plays a major role in controlling microRNAs also regulates the motivation to consume cocaine.
These microRNAs that are short stretch of RNA silencing genes were supposedly found to be crucial for cocaine addiction in mice. These findings may enable scientists to introduce novel means of fighting addictive diseases in humans. It has been assumed that the protein Argonaute 2 regulates the expression of messenger RNA that is the blueprint for protein production. The protein is able to control by either curbing or cutting messenger RNAs with complementary nucleotide sequences to certain microRNAs.
“Identification of miRNAs that contribute to addiction is just a first step in the research program that aims to identify the epigenetic mechanism of addictive behavior,” enlightened Anne Schaefer, a senior research associate in Paul Greengard’s Laboratory of Molecular and Cellular Neuroscience lead researcher.
The scientists elucidate that human and mouse genomes have four different forms of the Argonaute gene. It is believed that only Argonaute 2 is precisely able to curb messenger RNA expression. Previous analysis affirms that Argonaute 2 is capable of developing microRNAs from their precursors. Yet it is claimed to be selective and only affects a fraction of microRNAs in each cell.
Greengard, who is the Vincent Astor Professor remarked, “Our studies suggest that the important role of Argonaute 2 in cocaine addiction involves the presence or generation of specific microRNAs that contribute to stable changes in gene expression patterns that define neuronal cell plasticity and ultimately regulate the motivation to consume cocaine.”
In the course of the latest research, investigators scrutinized the Argonaute 2 protein for evaluating its role in a particular subset of neurons which are known to express the dopamine 2 receptor, called as Drd2. The properties of cocaine addiction are seemingly linked to its ability to boost levels of neurotransmitter dopamine. Elevation in dopamine levels may invite changes in the activity of dopamine receptors that takes place in the striatum region of the brain.
While conducting the experiment, researchers silenced the protein in mice with Drd2-expressing neurons. As a result, the mice’s motivation to self-administer cocaine seemed to have significantly declined. Also a peculiar group of microRNAs particularly controlled by Argonaute 2 in the striatum was discovered.
The scientists then employed a novel technique to examining cell-type specific microRNA. Argonaute 2-dependent microRNAs were compared to microRNAs enhanced in Drd2-neurons and upregulated in response to cocaine. This empowered the experts to lay hands on a set of 23 microRNAs possibly involved in cocaine addiction. Further investigations will be followed to affirm the findings.
The research is published online on July 19 in the Journal of Experimental Medicine.