Mice lacking a gene called NF1 are less prone to excessive drinking in an animal model, scientists have found. When the researchers looked at the same gene in humans, they found that variations in NF1 are linked with increased risk and severity of alcoholism.
Further work established that the NF1 gene regulates GABA, gamma-aminobutyric acid, a neurotransmitter important in determining mood.
'Despite a significant genetic contribution to alcohol dependence, few risk genes have been identified to date, and their mechanisms of action are generally poorly understood', said Vez Repunte-Canonigo, a staff scientist from The Scripps Research Institute (TSRI) in the USA, and co-author of the study.
The research team compared two groups of mice: one with the NF1 gene partially deleted, the other with intact NF1 genes. The mice underwent several different types of behavioural tests, which simulate alcoholism and include periods of withdrawal. The mice with partially deleted NF1 were found to be less susceptible to alcoholism.
In the second phase of the study, the team measured concentrations of GABA in the amygdala, a region of the brain that is implicated in the processing of decision making and emotional reactions such as stress- and addiction-related processes.
'As GABA release in the central amygdala has been shown to be critical in the transition from recreational drinking to alcohol dependence, we thought that Nf1 regulation of GABA release might be relevant to alcohol consumption', said TSRI Research Associate and co-author Dr Melissa Herman.
They found that NF1-lacking animals had lower levels of the neurotransmitter in the central amygdala, whereas alcohol consumption increased GABA levels in mice with functional NF1 genes.
As a final step, the team examined different variations of the NF1 gene in 9,000 people, and found that the gene was associated with a risk of alcohol dependence and the severity of alcoholism.
Commenting on the implications of the work, Dr Pietro Paolo Sanna, associate professor at TSRI and the study's lead author, said: 'A better understanding of the molecular processes involved in the transition to alcohol dependence will foster novel strategies for prevention and therapy'.
The NF1 gene gets its name from the disease neurofibromatosis type 1, a condition that causes tumours to grow along nerves.