Latha Karne is a junior majoring in Neuroscience and Behavioral Biology. She was awarded a Spring 2018 Independent Grant which she used to conduct research on opioid addiction under Dr. David Weinshenker.
Before entering college, students are required to take a series of tests to educate us on the dangers of abusing drugs. I've always known that prescription drugs should not be used by anyone except the individual for whom it was prescribed to, but had never seen up close the devastating effect that misuse can have. The summer before I started college, I was shadowing a trauma surgeon. A patient came in who was addicted to morphine, and I saw the difficulty of being able to treat their pain. Because the patient was addicted to a pain analgesic, he had developed a tolerance to the drug, which caused him to escalate his use and led to dependence. This “double hit” of the medication losing efficacy to treat the pain, while at the same time causing the addiction, was having a major impact on his health and quality of life.
What the doctor decided to do was treat the patient’s addiction, and give other pain medications to treat his pain. I kept asking the doctor whether there was a way to shut down the "addiction" part, while at the same time maintaining pain relief. I thought that it was strange to give a patient controlled substances that could feed their addiction, however the doctor explained that since the addiction was like a disease, he had to treat it to prevent withdrawals that would cause the patient even more pain. This stuck with me and I decided that I wanted to make an impact. Shortly after this, I started paying close attention to the opioid epidemic and saw the horrifying picture that went viral of the parents who overdosed on opioids and passed away in a car with a young boy in the backseat. This photo upset me and made me more passionate about wanting to find a treatment to help the people that are addicted to opioids. I realized that the best approach is to fully understand how opioids work in our brain and how the molecules and pathways are involved in compulsive drug use, and then design rational interventions based on science.
Drug self-administration protocols in labs are important for trying to mimic what is happening in human drug addicts to observe molecular changes in the brain. In my lab, we use rodents as a model organism to observe these changes. Traditionally, this involves surgically inserting a jugular catheter into the animal, then training it to press a level to receive intravenous drug infusions. While some opioids such as morphine and heroin are administered by humans into their veins, prescription opioids are often taken orally. In addition, rodents with catheters need to be singly housed so that their cage-mates do not disrupt their surgical site. Recently, I was introduced to a new behavioral apparatus called the Intellicage (image shown below). This system allows animals to be group-housed and orally administer a drug by poking their nose into an aperture to obtain access to a drug solution, and their behaviors are tracked using a chip implanted under their skin. My hope is that this apparatus will allow greater translatability to the human opioid epidemic due to the oral drug administration and the ability to house them as a group, since human drug users obviously interact with other people.
Currently, my project involves optimizing the parameters to carry out the self-administration tests in the Intellicage. The optimization phase involves confirming the dose of morphine solution that will be used for further testing and determining how hard the animals are willing to work to obtain the drug. The beginning was a struggle because no one had used this apparatus before in my lab, and I had to learn how to code the various programs that control the Intellicage. Given that the Intellicage uses custom coding software, there was no "Google search" to find the answers to various shortcuts and how the program worked. Once I got the Intellicage to be able to track the behaviors of the mice, I started performing a series of tests, where the mice were given access to two fluid bottles – one containing morphine + saccharin and the other containing either water or saccharin alone – to figure out how to make the mice prefer the drug solution. I added saccharin to sweeten the morphine because morphine tastes bitter and the mice won’t drink it by itself.
By working on this project, I have learned a lot about what it means to fail in research. There were many days when I was trying to teach myself how to program the Intellicage where the program would work one day, but then I would come back the next day and I could not get it to work. It is also difficult to work on something novel in the lab because there is no one I can ask when I run into problems – I have to figure things out on my own. Although this makes research seem difficult and sometimes frustrating, it is also very gratifying when I am able to overcome obstacles, and it makes me feel that I am doing something that could benefit patients like the ones I saw in the ICU.
Visit the Undergraduate Research Programs website to learn more about applying for Independent Research Grants.
Before entering college, students are required to take a series of tests to educate us on the dangers of abusing drugs. I've always known that prescription drugs should not be used by anyone except the individual for whom it was prescribed to, but had never seen up close the devastating effect that misuse can have. The summer before I started college, I was shadowing a trauma surgeon. A patient came in who was addicted to morphine, and I saw the difficulty of being able to treat their pain. Because the patient was addicted to a pain analgesic, he had developed a tolerance to the drug, which caused him to escalate his use and led to dependence. This “double hit” of the medication losing efficacy to treat the pain, while at the same time causing the addiction, was having a major impact on his health and quality of life.
What the doctor decided to do was treat the patient’s addiction, and give other pain medications to treat his pain. I kept asking the doctor whether there was a way to shut down the "addiction" part, while at the same time maintaining pain relief. I thought that it was strange to give a patient controlled substances that could feed their addiction, however the doctor explained that since the addiction was like a disease, he had to treat it to prevent withdrawals that would cause the patient even more pain. This stuck with me and I decided that I wanted to make an impact. Shortly after this, I started paying close attention to the opioid epidemic and saw the horrifying picture that went viral of the parents who overdosed on opioids and passed away in a car with a young boy in the backseat. This photo upset me and made me more passionate about wanting to find a treatment to help the people that are addicted to opioids. I realized that the best approach is to fully understand how opioids work in our brain and how the molecules and pathways are involved in compulsive drug use, and then design rational interventions based on science.
Drug self-administration protocols in labs are important for trying to mimic what is happening in human drug addicts to observe molecular changes in the brain. In my lab, we use rodents as a model organism to observe these changes. Traditionally, this involves surgically inserting a jugular catheter into the animal, then training it to press a level to receive intravenous drug infusions. While some opioids such as morphine and heroin are administered by humans into their veins, prescription opioids are often taken orally. In addition, rodents with catheters need to be singly housed so that their cage-mates do not disrupt their surgical site. Recently, I was introduced to a new behavioral apparatus called the Intellicage (image shown below). This system allows animals to be group-housed and orally administer a drug by poking their nose into an aperture to obtain access to a drug solution, and their behaviors are tracked using a chip implanted under their skin. My hope is that this apparatus will allow greater translatability to the human opioid epidemic due to the oral drug administration and the ability to house them as a group, since human drug users obviously interact with other people.
By working on this project, I have learned a lot about what it means to fail in research. There were many days when I was trying to teach myself how to program the Intellicage where the program would work one day, but then I would come back the next day and I could not get it to work. It is also difficult to work on something novel in the lab because there is no one I can ask when I run into problems – I have to figure things out on my own. Although this makes research seem difficult and sometimes frustrating, it is also very gratifying when I am able to overcome obstacles, and it makes me feel that I am doing something that could benefit patients like the ones I saw in the ICU.
Visit the Undergraduate Research Programs website to learn more about applying for Independent Research Grants.
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