Researchers have clearly established that a chemical dependence on alcohol occurs when repeated alcohol use changes the brain’s chemical requirements. However, they have never fully understood how alcohol exposure produces its characteristic alcoholism-related effects. In a study published in late 2013 in the journal Frontiers in Behavioral Science, researchers from several U.S. institutions explored the usefulness of a new technology, known as optogenetics, for improving the understanding of alcoholism’s effects. Their findings are the first to demonstrate a causal relationship between the release of dopamine in the brain and drinking behaviors of animals and could lead to powerful new ways to treat alcoholism.
Alcohol Dependence Basics
The human brain relies on a finely tuned mixture of certain vital chemicals (called neurotransmitters) to maintain its normal function. Any alteration of this mixture can have both short- and long-term repercussions in any given individual. When a person consumes alcohol, this mind-altering substance produces temporary changes in the usual balance of several neurotransmitters, including the pleasure-producing chemical dopamine. In a person who keeps his or her alcohol intake in the low-to-moderate range, the changes produced by drinking are fairly insignificant. However, in a person who transitions into occasional or regular heavy alcohol intake, the changes produced by drinking have a more profound effect. In an individual who regularly drinks excessively, the brain can switch from treating the presence of alcohol as an unusual situation to treating the presence of alcohol as an expected or required situation. As a rule, this switchover in the brain’s response heralds the onset of alcohol dependence or alcoholism.
Optogenetics is a term derived from two well-known words: optics and genetics. Scientists use this term to describe a new technology that lets doctors and researchers use targeted light to change the way that the genetic material contained inside the brain’s cells normally functions. Unlike previously developed methods for making therapeutic changes in brain function, optogenetics provides a very high degree of control and precision. This means that doctors and researchers can use optogenetics to improve their understanding of how the brain works, both in healthy people and in people affected by various disorders. It also means that doctors and researchers can potentially create highly specific treatments for a range of brain-related health problems. During some optogenetic procedures, researchers or doctors implant light-sensitive genes in the brain; once implanted, these genes respond to pulses of light and perform a predetermined task. Other optogenetic procedures rely on the natural responses that certain cells within the brain already have to light.
Usefulness for Understanding Alcoholism
In the study published in Frontiers in Behavioral Neuroscience, researchers from Wake Forest University, the State University of New York at Buffalo and the University of North Carolina at Chapel Hill used laboratory experiments with rodents to assess the usefulness of optogenetics for improving the level of scientific knowledge regarding alcoholism. In the experiments, rats were trained to drink alcohol in a way that mimics human binge-drinking behavior. First author Caroline E. Bass, assistant professor of pharmacology and toxicology in the School of Medicine and Biomedical Sciences, explains: “By stimulating certain dopamine neurons in a precise pattern resulting in low but prolonged levels of dopamine release, we could prevent the rats from binging. The rats just flat out stopped drinking,” she said. The researchers used implanted, light-carrying optical fibers to control certain pleasure-producing nerve cells in rodent brains that respond to the neurotransmitter dopamine. They chose to study dopamine because this chemical plays an important role in producing the brain effects that serve as a reward and incentive for the consumption of alcohol. The researchers found that they were able to control the targeted nerve cells in rodents by flashing pulses of blue laser light through the implanted optical fibers. After some experimentation, they also found that they could control and disrupt the specific chemical response inside these nerves that supports and promotes the continued consumption of alcohol.
Significance and Considerations
The results produced by the authors of the study published in Frontiers in Behavioral Neuroscience are important on two levels: first, they give scientists a better understanding of the precise chemical pathways that make the brain susceptible to alcoholism; in addition, they give scientists direct clues for developing future optogenetics-based treatments that disrupt the chemical cycle responsible for triggering alcoholism. In both respects, the information gained from optogenetics is substantially superior to the information gained from older, less precise methods of probing the brain and examining brain function. In addition, the study’s authors point out, the understanding provided by optogenetics gives doctors and researchers an improved awareness of the underlying mechanisms of an existing treatment for alcoholism called deep-brain stimulation.