Role of ventral subiculum neuronal ensembles in incubation of oxycodone craving after electric barrier–induced voluntary abstinence
Ida Fredriksson, Pei-Jung Tsai, Aniruddha Shekara, Ying Duan, Sarah V. Applebey, Angélica 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
Abstract
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.