Lighting Up Brain Stops Liquored-Up Rats

Stimulating brain cells with light stops binge drinking in rodents, a new study finds. The results suggest the possibility of using optogenetics to treat substance abuse, neurological diseases and mental illnesses.

A team at the University at Buffalo used light to stimulate neurons in rodents that had been trained to drink alcohol in a way that mimics human binge-drinking. The work is the first to demonstrate a causal relationship between the release of dopamine in the brain and the drinking behaviors of animals, and helps explain the underlying neurochemical basis of drug addiction.

"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," said Caroline E. Bass, Ph.D., assistant professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences.

The rodents continued to avoid alcohol even after the stimulation of neurons ended, she added.

“For decades, we have observed that particular brain regions light up or become more active in an alcoholic when he or she drinks or looks at pictures of people drinking, for example, but we didn’t know if those changes in brain activity actually governed the alcoholic’s behavior,” she said.

The team activated the dopamine neurons through a type of deep-brain stimulation, but unlike techniques now used to treat certain neurological disorders, such as severe tremors in Parkinson’s disease patients, optogenetics uses light instead of electricity to stimulate neurons.

“Electrical stimulation doesn’t discriminate,” Bass said. “It hits all the neurons, but the brain has many different kinds of neurons, with different neurotransmitters and different functions. Optogenetics allows you to stimulate only one type of neuron at a time.”

Bass specializes in using viral vectors to study the brain in substance abuse. In this study, she used a virus to introduce a gene encoding a light-responsive protein into the animals’ brains. That protein then activated a specific subpopulation of dopamine neurons in the brain’s reward system.

“I created a virus that will make this protein only in dopaminergic neurons,” Bass said.

The neuronal pathways affected in this research are involved in many neurological disorders, she said. For that reason, the results have application not only in understanding and treating alcohol-drinking behaviors in humans, but also in many devastating mental illnesses and neurological diseases that have a dopamine component.

This ability to target genes to dopamine neurons could potentially lead to the use of gene therapy in the brain to mitigate many of these disorders, she said.

“We can target dopamine neurons in a part of the brain called the nigrostriatal pathway, which is what degenerates in Parkinson’s disease,” she said. “If we could infuse a viral vector into that part of the brain, we could target potentially therapeutic genes to the dopamine neurons involved in Parkinson’s. And by infusing the virus into other areas of the brain, we could potentially deliver therapeutic genes to treat other neurological diseases and mental illnesses, including schizophrenia and depression.”

Research such as this, which makes it possible to map the neuronal circuits responsible for specific behaviors, is a major focus of President Barack Obama’s Brain Research for Advancing Innovative Neurotechnologies initiative (BRAIN).

The research was funded by the National Institutes of Health and is published in Frontiers in Behavioral Neuroscience.

For more information, visit www.buffalo.edu.