Neurobehavioral Consequences of Early Opioid Exposure: Molecular and Behavioral Analysis

Mouse with litter

Students

COL 2021
College

Faculty

Professor of Pharmacology

Project Summary

Thanks to the grant I received from the Penn Undergraduate Research Mentoring Program, I was able to participate in a project that assesses the mechanisms and consequences of early opioid exposure in neonatal mice. The opioid crisis is steadily increasing, and this internship allowed me to expand my knowledge on the subject of Neonatal Abstinence Syndrome as well as investigate first-hand the effects of this type of drug dependency. Working under Dr. Julie Blendy and Dr. Shivon Robinson as mentors, I learned many valuable laboratory techniques such as animal handling, drug administration, and quantitative behavioral analysis.

The goal of this study was to 1) determine the effects of early morphine exposure on the emergence of developmental milestones in neonatal mice, and 2) characterize withdrawal symptoms that occur after chronic early opioid exposure. Considering the differences in withdrawal symptoms between infants and adults (in both rodents and humans), it is important that we investigate opioid dependence specifically in neonatal animals. In our study, neonatal mice were treated with either morphine or saline for two weeks starting on the day of birth. On day 14, all mice were injected with naloxone, a drug that rapidly blocks their opioid receptors, initiating precipitated withdrawal. Weight was recorded from PND1-14, as well as developmental milestones, ultrasonic vocalizations, body temperature, and withdrawal behaviors. Our findings indicate that the administration of morphine from PND 1-14 blunts weight gain and delays developmental milestones. Furthermore, when given a mu-opioid receptor antagonist (naloxone) on PND 14, morphine treated mice exhibit precipitated withdrawal symptoms.

A second study that stemmed from our initial goals involved determining what role the immune system plays in withdrawal. Previous studies in the lab had shown that early morphine exposure increases immune response in the brain. Together with morphine, we co-administered an antibiotic as well as an anti-inflammatory medication to see how developmental milestones and withdrawal were affected. After analyzing development, weight, core body temperature, and withdrawal behaviors, our results show that co-administration of these two drugs did not have an effect on the emergence of developmental milestones and did not attenuate withdrawal symptoms.

The accessible undergraduate research opportunities at Penn were one of the main reasons I decided to apply; a goal coming in as a freshman was to intern for a laboratory that focuses on the central nervous system. I have learned so much from my hands-on experience, and I was given the opportunity to commit to a project and see it progress. The skills I have acquired from working in a laboratory are not only translational to other jobs in the future, but they have also supplemented my studies. Considering I am a BBB (Biological Basis of Behavior) major, the work that I have done this summer has expanded my knowledge in the field and has given me a preview of studies that are available to me.