Authors: Ida Fredriksson, Pei-Jung Tsai, Aniruddha Shekara, Ying Duan, Sarah V. Applebey, Angelica Minier-Toribio, Ashley Batista, Jonathan J. Chow, Lindsay Altidor, Estelle Barbier, Carlo Cifani, Xuan Li, David J. Reiner, F. Javier Rubio, Bruce T. Hope, Yihong Yang, Jennifer M. Bossert, Yavin Shaham
Published: 2023-01-11
Source: Full article
High relapse rate is a key feature of opioid addiction. In humans, abstinence is often voluntary due to negative consequences of opioid seeking. To mimic this human condition, we recently introduced a rat model of incubation of oxycodone craving after electric barrier–induced voluntary abstinence. Incubation of drug craving refers to time-dependent increases in drug seeking after cessation of drug self-administration. Here, we used the activity marker Fos, muscimol-baclofen (GABAa + GABAb receptor agonists) global inactivation, Daun02-selective inactivation of putative relapse-associated neuronal ensembles, and fluorescence-activated cell sorting of Fos-positive cells and quantitative polymerase chain reaction to demonstrate a key role of vSub neuronal ensembles in incubation of oxycodone craving after voluntary abstinence, but not homecage forced abstinence. We also used a longitudinal functional magnetic resonance imaging method and showed that functional connectivity changes in vSub-related circuits predict opioid relapse after abstinence induced by adverse consequences of opioid seeking.