Effect of PV Interneurons on Opioid Withdrawal

Abstract

Since the opioid epidemic first started in the 1990’s, it’s societal impact has exponentially increased. With reports of 11.4 million people misusing opioids, understanding the mechanisms behind abuse and addiction is more critical to public health than ever. Our lab has previously shown that parvalbumin (PV)-fast spiking interneurons (FSI) are active during opioid withdrawal. In order to further elucidate the behavioral effect of PV activity, mice were virally injected with either Kir 2.1, a virus that turns off PV interneurons by turning off their K+ channels, or YFP, a fluorescent tag used as the control. These mice then underwent a Conditioned Place Aversion (CPA) assay, which is commonly used to measure a drug’s negative reinforcing properties. In the CPA mice were implanted with osmotic mini pumps that continuously delivered either morphine (opioid) or saline (control) and underwent a baseline, three conditioning days, and a test. The baseline and test exposed mice to two novel environments simultaneously and time spent on either environment was recorded. During conditioning, mice were exposed to only one environment and received injections of naloxone (opioid receptor antagonist), pairing the environment with withdrawal. Aversion was measured as decreased spent on the naloxone- paired side on the test as compared to baseline. Kir 2.1 animals showed a decreased naloxone aversion in the CPA as compared to the controls, indicating that PV-interneurons are required for learning an aversive response to withdrawal. This helps us better understand the mechanisms behind opioid abuse and addiction and can be used to develop future treatments.