Extensive opioid use and repeated abstinence increases the likelihood of severe withdrawal and contributes to the risk of relapse. Previously we found that microglia, the innate immune cells in the brain, have dramatic changes in gene expression and signaling during opioid tolerance and withdrawal. We propose to use fentanyl and a recently developed transgenic mice to investigate whether repeated cycles of tolerance and withdrawal aggravate changes in microglial function and whether purinergic receptors in microglial contribute to opioid withdrawal. We will study the microstructure and motility of microglia using time- lapse microscopy and measure real-time changes in cyclic and calcium dynamics. The goal of the project is to identify new targets to treat opioid withdrawal and relapse.
August 1, 2021 — June 30, 2024
Substance use disorders/misuse