Like all addictions, alcoholism is a complex and enigmatic issue, often sparked by a combination of causes ranging from psychological trauma and environmental influences to genetic factors. To investigate the connection between alcoholism and DNA, scientists from Purdue and Indiana University have analyzed the genome of alcoholic rats, discovering that the number of genes associated with the condition far exceeds expectations.
Though rats don’t tend to enjoy the taste – or the effects – of alcohol, there are always a few exceptions in every population, so the researchers kept an eye out for rats that appeared more partial to a drink than their peers. By breeding these rats over several generations, the scientists were eventually able to create a line of rodents with a natural taste for alcohol.
Describing their work in the journal PLOS Genetics, the study authors reveal how they compared the genomes of booze-loving rats to those that lacked this preference. In doing so, they were able to identify 930 different genes that appear to be associated with alcoholism.
“It’s not one gene, one problem,” explained study co-author William Muir in a statement, adding that “this trait is controlled by vast numbers of genes and networks. This probably dashes water on the idea of treating alcoholism with a single pill.”
Interestingly, the majority of the genes identified as being involved with alcoholism were found in regulatory regions of DNA rather than coding regions. This means that they do not directly code for the creation of proteins, but instead control how prominently other coding genes are expressed.
Many of the genes identified as being associated with alcoholism do not actually code for proteins, but merely regulate the expression of other genes. adike/Shutterstock
The fact that these 930 genes were so widespread throughout the genome suggests that tackling alcoholism may require a holistic approach, rather than focusing on a single physiological process. However, the researchers found that a large number of these genes were involved in the glutamate receptor signaling pathway, and therefore suggest that this may be a good place to start.
Glutamate is a neurotransmitter that is mainly picked up by receptors called NMDA receptors, which are found on the membranes of neurons. When stimulated, these receptors increase the excitability of neurons, while other receptors that receive a neurotransmitter called GABA offset this effect by inhibiting these neurons. As such, the neurons in the brain’s reward circuit are regulated by a delicate balance between excitation and inhibition, and upsetting this balance can often lead to the development of addictive behaviors.
Since several of the genes identified in this study are associated with NMDA receptors, it seems likely that developing treatments that target this pathway could help to attenuate alcoholism.
It is worth noting, however, that more work will be required in order to determine if the same genes found in rats are also associated with alcoholism in humans.
