The researchers say that lack of the PRDM2 enzyme in the prefrontal cortex decreases impulse control in animals and may therefore contribute to continued alcohol abuse, even when continued use has adverse physical and mental consequences. The study is the first to identify the molecular mechanism of PRDM2 in the brain, as this enzyme was previously studied in cancer research.
Professor Markus Heilig from the University of Linköping in Sweden and lead author of the study, said: 'We see how a single molecular manipulation gives rise to important characteristics of an addictive illness. Now that we're beginning to understand what’s happening, we hope we'll also be able to intervene'.
The researchers conducted a series of studies, which were published in Molecular Psychiatry. In the first study, rats were made alcohol-dependent and their brain tissue was analysed. The alcohol-addicted rats had reduced levels of the PRDM2 enzyme in the frontal cortex. This effect was detectable weeks after the alcohol exposure had been discontinued.
In the second study, the researchers knocked out the expression of the PRDM2 enzyme in rats that were not alcohol-dependent. The rats showed the same loss of impulse control as the alcohol-dependent rats. Rats with reduced PRDM2 levels displayed signs of addiction in that they continued to seek up alcohol even when it was associated with adverse effects, such as bitter taste or electric shocks.
'PRDM2 controls the expression of several genes that are necessary for effective signalling between nerve cells. When too little enzyme is produced, no effective signals are sent from the cells that are supposed to stop the impulse,' Professor Heilig said.
It has long been suspected that frontal lobe function is impaired in alcoholism but this study is among the first to indicate how impairment happens at a molecular level, pointing to a specific and previously unknown epigenetic mechanism. However, as this study was conducted in rats, it is as yet unknown if the results would generalise to humans.
The researchers say the ultimate goal of this research is to develop new treatments for alcoholism and, in the shorter term, also to help reduce the stigma associated with alcohol-dependence.
'Over the long term, we want to contribute to developing effective medicines, but over the short term the important thing, perhaps, is to do away with the stigmatisation of alcoholism,' said Professor Heilig.