From The Editor | January 24, 2014

Optogenetics Helps Binge-Drinking Rats Sober Up

By Clinton Shaffer

What if I told you that flashing lights could one day cure alcoholism?

A recent study published by a team of researchers at the University of Buffalo has demonstrated that the technique is not only possible, but very effective — in binge-drinking rats.

For the experiments, rodents were trained to habitually consume alcohol in a manner consistent with human binge-drinking behavior. Researchers then used optogenetic techniques in order to manipulate the release of dopamine in the rats’ brains, and put an end to their vices.

The treatment was so effective that, even after the light stimulation, the rodents completely avoided alcohol.

Optogenetics involves the use of light to stimulate cell behavior. In these experiments, researchers used a laser to deliver blue light pulses in order to activate the dopamine neurons of the rodents’ reward system, which, in turn, deterred their drinking habits.

Researchers tested the rats using both high frequency and low frequency stimulation. The high frequency testing exposed the neurons to 50 light pulses at 50 Hz with 30 second intervals, while the lower frequency testing used 250 light pulses at 5 Hz with 1 second intervals. The team used a Systron Donner pulse generator (Model 100C) to produce the light pulses, controlling the number of pulses with an SMS digital delay generator (Model DG535). For the optical delivery, the researchers used a 473 nm wavelength Viasho laser with a power output of 1 ~ 100 mW, monitoring the power output with a Newport power meter (Model 1815C).

The researchers found that the lower frequency stimulation stemmed the rats’ drinking impulses. Caroline E. Bass, Ph.D., lead author of the study, explained: “By stimulating certain dopamine neurons in a precise pattern [250 light pulses at 5 Hz with 1 second intervals], resulting in low but prolonged levels of dopamine release, we could prevent the rats from binging. The rats just flat out stopped drinking.”

Neurons, however, are not naturally sensitive to light, so genetic engineering was required for the technique to work. For the study, Bass and colleagues from Wake Forest University fabricated “a virus to introduce a gene [that encoded] a light-responsive protein into the animals’ brains.”

The virus formed the light-responsive protein in only a targeted group of the rats’ dopaminergic neurons. So, when the rats were exposed to the intermittent bursts of light, only those specific cells were activated. The ability to target specific groups of cells is a huge advantage over other techniques, like electrical stimulation, which stimulates brains cells indiscriminately.

While the study is the first to display the connection between the drinking behaviors of animals and the release of dopamine in the brain, it has much greater implications than just helping alcoholic rats go cold turkey.

According to the University of Buffalo news release, the work could be significant for developing “powerful new ways to treat alcoholism, other addictions, and neurological and mental illnesses”— like depression, Parkinson’s disease, and schizophrenia. The findings also help to “explain the underlying neurochemical basis of drug addiction.”

The study was funded by the National Institutes of Health and is aligned with President Obama’s BRAIN (Brain Research for Advancing Innovative Neurotechnologies) initiative.