"Revolutionary Neuroscience Technique Slated for Human Clinical Trials" is an article in the Scientific American journal that highlights the great effects optogenetics could have on neuroscience research. Generally, optogenetics is a technique where one can activate or inhibit specific neurons in specific brain areas using opsin proteins. As of right now most of the research has been done in only animal models because of the invasive procedures. However, in the coming years, professionals wish to start human clinical trials with optogenetics to treat chronic pain. The biggest obstacle with human trials is how to insert the opsin genes into human neurons. The article discusses different strategies to accomplish this in a safe way, with the most promising strategy being the use of a virus to insert genes into the neurons. There are still many issues with the idea, but it's a starting point. Although these trials aim to use optogenetics to help with chronic pain, if they develop a way to safely insert opsin proteins into human neurons, the technique can be applied in many other areas of research, including opioid addiction.
Dr. Stephen Steidl gave a talk on his optogenetics research, dealing specifically with the opioid reward system. He does studies in rats and mice where he selectively targets mesopontine inputs to the VTA. The VTA is a part in the brain with many neurons that synapse on the Dopamine system, which is said to be crucial in the reward effect of opioids. In science, there are not many conclusions on what inputs to the VTA directly affect the Dopamine reward system and what effects those inputs have. Dr. Steidl focuses on LDTg neurons, which are mesopontine nuclei that input to VTA neurons that may influence the DA reward system. In the experiments, an opsin protein called ChannelRhodopsin2 was inserted surgically into LDTg neurons in the rodent brain. This specific opsin protein is activated by a blue light, so shining a blue light into the rodent brain would exclusively activate LDTg neurons. Through operant conditioning experiments, rats showed a preference for the blue light and would constantly press a lever to attain more of the light. Through micro dialysis, they found that Dopamine levels were higher than usual during this self-administration of blue light. These facts together show that these LDTg neurons do in fact play a part in the reward system.
The next step in his research was to experiment with actual opioids given to rodents to simulate opioid addiction in humans. One experiment he does is a Conditioned Place Preference Test. This is when a rodent is continuously given a drug in one chamber and saline in another chamber that looks and feels different than the first. After conditioning the rodent to this schedule, it is let free between the two chambers to choose which side it prefers. Control mice will almost always develop a preference for the chamber in which they received the drug. Optogenetics comes into place because with genetically modified rodents, researchers can activate or inhibit the neurons they choose to study. In this case, LTDg neurons can be inhibited and one can see if the rodent still develops a preference to the drug. The results of those optogenetic experiments can suggest just how crucial these neurons are to the rewarding effects of the drug. These types of experiments are critical in determining how opioids affect the brain and where the rewarding effects come from.
Dr. Steidl's research has shown the possibility for rodents to take a drug (specifically morphine), but not experience the reward effects associated with it. If we were able to apply techniques discussed in the Scientific American article, there is a possibility we would be able to insert the same opsin proteins into the VTA neurons in humans. With the same type of techniques used in rodents, it could be possible to inhibit certain neurons associated with opioid reward. For most people, taking away the rewarding effect of the drug takes away the reason to keep self-administering. This could eventually turn into a treatment for people suffering from addiction. As stated in "The Worst Drug Crisis in American History" in the New York Times, the opioid crisis is dangerous and lethal. It touches on how hard recovery is, calling it a "steep uphill climb". A main obstacle in recovery is the craving for the rewarding effects such as euphoria. Treatments developed from research like Dr. Steidl's could extinguish these rewarding effects and create an easier recovery system for addicts, combating the opioid crisis.
Works Cited
Bruder, Jessica. “The Worst Drug Crisis in American History.” The New York Times, The New York Times, 31 July 2018, www.nytimes.com/2018/07/31/books/review/beth-macy-dopesick.html.
Sutherland, Stephani. “Revolutionary Neuroscience Technique Slated for Human Clinical Trials.” Scientific American, 5 Jan. 2016, www.scientificamerican.com/article/revolutionary-neuroscience-technique-slated-for-human-clinical-trials/.
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