Exploring how dopamine neurons in the ventral tegmental area (VTA) of the brain influences alcohol drinking behaviours, a study at the University at Buffalo (UB), New York (US), has found that the emerging technique of optogenetics can stop binge drinking in rodents, suggesting gene therapy in the brain could be used to treat substance abuse, drug addiction, neurological diseases and mental illnesses.
“We know that dopamine neurotransmission is linked to [alcohol drinking] behaviours, but we did not know how,” says Caroline E. Bass, PhD, Assistant Professor of Pharmacology and Toxicology in the UB School of Medicine and Biomedical Sciences. “Optogenetics allows us to stimulate the dopamine neurons directly, to see if dopamine release can actually modify drinking.” Optogenetics introduces a light-sensitive protein (opsin) into the neuron. When exposed to light the protein causes the neuron to fire and release neurotransmitter. “In this paper, one innovation is that we were able to target this light sensitive protein to only dopamine neurons,” Bass says. She is referring to the article “Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration,” published in Frontiers in Neuroscience, for which she served as first author.
Bass has no doubt optogenetics has already “revolutionised” neuroscience. “We can now do more than just measure neurotransmitter release or neuronal activity when a behaviour is happening,” she says. “We can induce release and see if it actually causes a behaviour.”
According to the pharmacology and toxicology expert, it is difficult to know which area of the brain is responsible for which behaviour. “Optogenetics allows us to parse this out,” says Bass. “We can stimulate a brain region to see how this alters behaviour and begin to map behaviours in a very precise way to the brain.” This ability to stimulate neurons with light could lead to better understanding of how to target these brain regions for developing treatments.
Bass’ pioneering work could help propel optogenetics to the next level. “One of the important aspect of this study is showing how opsins can be targeted to specific neurons in normal animals,” she says, explaining that most previous optogenetics studies have used mutant mice that come pre-engineered with opsin-induced neurons. The UB team, however, used rats and were able to target the opsin only to dopamine neurons. “This is important because it opens up the field to other experimental models, and it gives us an avenue for targeting opsins to humans,” Bass interprets. “In the future we may be able to treat many dopamine-based disorders, including Parkinson's disease, schizophrenia and addiction using this technique.”
In the study, the test animals, rats, were trained to drink alcohol in a way that mimics human binge-drinking behaviour. “I was most surprised that low-level dopamine release prevented the animals from drinking long after we stopped stimulating the neurons,” Bass says. “This points to a lot of potential behavioural mechanisms involved in how dopamine influences drinking.”
Bass and her team still have many questions, such as which regions of the brain are most relevant to drinking alcohol? Would they see similar results with other drugs of abuse, such as cocaine? The team also want to extent their technique to targeting other types of neurons. “The brain is like a gigantic puzzle and it's tools like these that will help us put the pieces together,” Bass says. “We are on the cusp of truly transformative studies in neuroscience.”
Written by Sandra Henderson, Research Editor Novus Light Technologies Today