Previous research has implicated the brain's opioid system in the development of alcohol-use disorders. The mu-opioid receptor, which is encoded by the OPRM1 gene, is the primary site of action for opiates with high abuse potential, such as opium and heroin, and may also contribute to the effects of non-opioid drugs, such as cocaine and alcohol. Findings published in the December issue of Alcoholism: Clinical & Experimental Research indicate that individuals with the G variant of the A118 polymorphism of the OPRM1 gene have greater subjective feelings to alcohol's effects as well as a greater likelihood of a family history of alcohol-use disorders.
"Alcohol releases endogenous opiates which, in turn, seem to influence the mesolimbic dopamine system," said Kent E. Hutchison, associate professor of psychology at the University of Colorado at Boulder and lead author of the study. "This system is involved in craving and the motivation to use alcohol and drugs. Thus, it is alcohol's effects on endogenous opioids that act as the gateway through which alcohol may influence this system."
"It is well known that alcohol dependence tends to run in families," said Robert Swift, professor of psychiatry and human behavior at Brown University and Associate Chief of Staff for Research at the Providence VA Medical Center. "The inheritance of alcoholism is complex, but there are suggestions that the opiate systems in the brain are involved. Our brains contain proteins, called enkephalins and endorphins, that act like morphine and other opiates derived from the poppy plant. Several researchers have shown that persons with a family history of alcoholism tend to have differences in blood levels of beta-endorphin, a natural opiate hormone, compared to persons without a family history of alcoholism. Children of alcoholics, who are not themselves alcoholics, have lower levels of beta-endorphin than do children of non-alcoholics. Also, when young adults with a family history of alcoholism drink alcohol, they increase their blood levels of beta-endorphin more than those without a family history of alcoholism."
A special protein called the mu-opioid receptor, which is located in the membranes of nerve cells, detects internal opiate neurotransmitters, such as beta-endorphin, that the brain uses to allow nerve cells to communicate with each other. Previous research has shown that the G variant of this gene has a slightly different receptor protein, which causes a big difference in how well the receptor connects with beta-endorphin. For example, the G variant receptor binds three times more tightly than the A variant to beta-endorphin, which means that a nerve cell with the G variant is more greatly affected by beta-endorphin. The net result is that dopamine cells, which play a role in motivation and reinforcement, become more stimulated.
For this study, participants comprised 38 students (20 male, 18 female) at the University of Colorado, 21 to 29 years of age, who indicated drinking patterns classified as moderate to heavy. Participants were either homozygous for the A allele (n=23) or heterozygous (n=15). Each received intravenous doses of alcohol that were designed to cause breath alcohol concentration (BAC) levels of .02, .04, and .06. Researchers measured subjective intoxication, stimulation, sedation, and mood states at baseline and at each of the three BAC levels.
Results indicate that individuals with the G allele had higher subjective feelings of intoxication, stimulation, sedation, and happiness across trials as compared to participants with the A allele.
The OPRM1 gene is likely one of dozens of genes that influence the odds that a person who drinks alcohol will eventually become an alcoholic. Once DNA sequencing costs fall a couple more orders of magnitude all the genes that influence the risk of alcoholism (and the risks of all other diseases - addictive or otherwise) will be identified in short order.
The identification of genes that are involved in addiction will eventually lead to the development of drugs that suppress and increase their expression and other drugs that work at receptors that the genes code for. As a result addiction will become much more easy to treat and even to cure.
|Share |||Randall Parker, 2004 December 14 02:48 PM Brain Addiction|