Tag: addiction

Although the effects of alcohol have been enjoyed around the world for thousands of years, addiction can lead to significant social and medical problems. Alcohol affects a number of different biochemical pathways and a better understanding of the factors that contribute to alcohol abuse and addiction could lead to improved treatments. Since a lower initial response to the effects of alcohol has been found to correlate with increased risk of future alcoholism, identification of the genes and pathways involved in the acute response might throw light on the genetic factors contributing to addiction. The fruit fly, Drosophila melanogaster, reacts in much the same way as mammals to acute ethanol exposure and a team led by Ulrike Heberlein at the University of California is using the fly to explore the links between genetic make-up and response to alcohol. Their latest find is that flies with a mutant version of a gene that they have designated ‘happyhour’ are less sensitive to the sedative effects of alcohol than flies with a normal copy of the gene. Further studies showed that the epidermal growth factor (EGF)-signalling pathway regulates ethanol sensitivity in Drosophila and that the happyhour protein inhibits this pathway.

The EGF receptor (EGFR) is overexpressed in certain types of carcinoma and drugs that inhibit the EGFR tyrosine kinase such as erlotinib (Tarceva™) and gefitinib (Iressa™) have been successfully developed for the treatment of cancer. The team were able to show that treatment with erlotinib increased acute alcohol sensitivity in both fruit flies and mice and, importantly, also reduced alcohol consumption in a rat model of alcoholism. Although it is not yet clear exactly how alcohol exerts its influence on the EGF pathway or how these changes lead to changes in behaviour after alcohol consumption, the authors suggest that inhibition of the pathway could provide a potential treatment for alcohol addiction. Both erlotinib and gefitinib are well-tolerated and are known to cross the blood-brain barrier. The study is published in the journal Cell.

At this time of year many smokers will be trying to quit, and a recent study suggests that some will find it harder than others. Most smokers believe that smoking improves concentration and, undoubtedly, withdrawal symptoms cause feelings of irritability and agitation that make concentration difficult. When nicotine levels fall, smokers experience withdrawal symptoms which can only be alleviated by another cigarette. Scientists at the Abramson Cancer Center and Department of Psychiatry in the University of Pennsylvania School of Medicine had previously shown that smokers with a polymorphism in the catechol-O-methyltransferase (COMT) gene that results in a methionine to valine substitution suffer more from concentration problems associated with nicotine withdrawal. COMT is one of a number of enzymes that degrade catecholamines such as dopamine, and individuals with the valine COMT variant degrade dopamine at a faster rate than those with the methionine variant. The group has now used functional magnetic resonance imaging to examine brain function in smokers both during periods of abstinence and normal smoking. During the brain scans, the subjects were asked to hold in their minds a series of complex geometrical figures. The results showed that smokers with the valine variant suffered greater deficits in working memory and brain function when they had refrained from smoking for 14 or more hours, and this group also reported more severe withdrawal symptoms. The findings are published in the journal Molecular Psychiatry.

Smokers with the valine COMT variant are less responsive to existing therapies for smoking cessation and the study suggests that this group could be helped to quit by COMT inhibitors.