28 February 2011

Neuroscience of Binge Drinking Better Understood

[M]anipulating two receptors in the brain, GABA receptors and toll-like receptor 4 (TLR4), "caused profound reduction" of binge drinking for two weeks in rodents that had been bred and trained to drink excessively." The study was published online the week of Feb. 28 in the journal the Proceedings of the National Academy of Sciences.

About 30 percent of Americans who drink do so excessively, and about 75,000 people die each year from the effects of excessive drinking. Current treatments for excessive alcohol drinking include prescription drugs Revia and Campral for controlling cravings. To ease withdrawal symptoms, doctors often prescribe medications such as Valium and Librium that carry their own risks of addiction. Valium and Librium reduce the anxiety alcoholics feel when they stop drinking but do not reduce cravings for alcohol.

The new study found that treatments that manipulate both the GABA receptor and toll-like receptor 4 have the potential to reduce anxiety and control cravings, with little to no risk for addiction[.] . . .

GABA receptors are a class of receptors in the brain that react to the neurotransmitter GABA and act as inhibitory receptors, calming down or inhibiting the activity of neurons in the brain. GABA receptors react to alcohol, giving drinkers a calm and euphoric feeling and reinforcing excessive drinking behavior. . . . This is the first scientific study to document GABA receptors' key involvement in binge drinking specifically, though scientists already believed that the receptors had a role in excessive drinking in general. . . .

Science has traditionally considered TLR4 to be an innate immunity receptor involved with neuroinflammation in the brain. Scientists associated TLR4 with microglia, cells that support inflammatory responses in the brain. "What makes this finding particularly important for the field of neuroscience is that we're showing that TLR4 plays a significant role in neurons, specifically, the neurons that are connected to the GABA receptor," . . . . To establish the connection between the GABA receptors, TLR4 and alcohol, the scientists manipulated this pathway in the binge drinking rodents . . . [with] a herpes viral vector . . . to deliver a gene-modifying agent directly to the neurons in the brain, to target TLR4 and GABA receptors. The scientists found that when they artificially stimulated the GABA receptors and TLR4 in order to simulate the good feelings binge drinkers feel when drinking alcohol, the rats lost interest in alcohol for two weeks after the procedure.

Compounds exist that would stimulate the receptors in the same way the scientists did in the study. "It's very likely that, down the road, these compounds could become new therapies for binge drinking . . . These compounds would act like a substitute for alcohol, much like methadone acts as a substitute for heroin. They would help alcoholics stop drinking, giving them relief from their cravings and from the anxiety that they try to alleviate with drinking."

From here.

So, drugs to end a predisposition to binge drink may be on the horizon in our near future, and there is a methodological precedent for determining a cause and developing a treatment for other kinds of substance addictions.

Given the strong connection between alcoholism and other kinds of substance abuse, and a wide range of socially unacceptable behavior and crimes, the next question is whether these treatments promise a world in which those social ills are dramatically less of problem.

Also, if such drugs existed, what would it take to get binge drinkers to take it? Will drug testing for probationers cease to become a matter of seeing that they aren't taking illegal drugs and become a matter of confirming that they are taking drugs that treat their vulnerabilities?

Given the poor track record of science at observing ethical standards with vulnerable or institutionalized populations, there is also good reason to fear abuses along the same lines in the future.

There may also be an upside to the complexity of many polygenetic mental health traits. While it may take just a single disruption of one of thousands of genes that go into a health functioning brain, if dysfunctional processes are equally complex, a single way to disrupt that process may deal with problems that have a wide variety of causes. This seems to be the story of modern psychiatry. We have found drugs that can manipulate a handful of neurochemicals in the brain, but those drugs treat a large number of patients with neurochemical imbalances in the neurochemical systems that most commonly go awry.

Drugs that act on neurochemical receptors and reuptake channels seems to address a great many mental health conditions. This part of the brain seems particularly succeptable to treatment with drugs. There may be other parts of the brain that are equally important, perhaps miswired neurons, for example, but we don't understand how to treat them as well.

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