Discovering the brain’s role in alcohol dependence

Addiction is a debilitating brain disease that results in a physical and psychological dependence on a substance or behavior. The prolonged use of alcohol can result in an addiction—known as alcohol use disorder—that affects 14.1 million adults in the United States. Although a variety of psychological, genetic and behavioral factors can cause dependence on alcohol, many experts believe that the connection between brain cells (also called neurons) plays a major role.

Researchers from the Texas A&M University School of Medicine have discovered the essential distribution patterns of other brain cells connecting to two types of neurons expressing dopamine receptors (D1 or D2) in a brain region called the dorsomedial striatum. These D1 or D2-containing striatal neurons have distinct behavioral effects—a D1, or the “go” neuron, and the D2, or the “no-go” neuron. These findings will help provide a solid foundation for future studies on the brain’s role in alcohol addiction. Their research was published in the journal eNeuro.

“These studies are quite important because many people suffer from alcohol use disorder,” said Jun Wang, MD, PhD, associate professor in the Department of Neuroscience & Experimental Therapeutics at the Texas A&M School of Medicine and lead author of the study. “Alcohol is widely used because it is a legal substance, but unfortunately, people can develop dependence, so we want to better understand what drives that process. We focus on the brain because we think the brain controls behavior.”

Wang’s previous work explains that D1 neurons (“go” neurons) compel or motivate a person to do something, such as drink alcohol, while D2 neurons (“no-go” neurons) discourage or stop a person from doing something, such as stopping drinking alcohol. His previous findings show that D1 neurons play an important role in alcohol addiction.

For this study, Wang and his team wanted to discover which parts of the brain drove the activity of D1 and D2 neurons.

Although there are many different areas in the brain, Wang and his team focused on examining the dorsomedial striatum (also known as part of the basal ganglia) in animal models. The reason they studied this area specifically is because it plays a critical role in the control of goal-directed actions and drug-seeking behaviors, Wang said.

Using a special technique called rabies virus-mediated retrograde monosynaptic tracing to map the brain-wide direct inputs to D1 or D2 neurons, Wang and his team discovered that the D1 neurons preferentially received input information from the cortex—which is part of the brain involved in motivational and decision-making behaviors. At the same time, D2 neurons mainly received information from the thalamus, which is involved in behavioral flexibility. The behavioral flexibility is critical for preventing excessive and compulsive drinking.

“This means that excessive alcohol intake may enhance cortical information inputs to striatal “go” neurons and suppress thalamic inputs to striatal “no-go” neurons,” Wang said. “Thus, we may reduce excessive alcohol drinking by inhibiting cortical inputs and enhancing thalamic inputs.”

Wang believes this research will provide a better foundation for future studies in helping to better understand the dorsomedial striatum and its role in alcohol addiction. “It’s good to have a baseline of how these neurons are distributed in the brain so we can learn more about the dorsomedial striatum, since it plays a very big role in addiction,” he said.