학술논문
Role of ventral subiculum neuronal ensembles in incubation of oxycodone craving after electric barrier-induced voluntary abstinence
Document Type
Author
Fredriksson, Ida; Tsai, Pei-Jung; Shekara, Aniruddha; Duan, Ying; Applebey, Sarah V.; Minier-Toribio, Angelica; Batista, Ashley; Chow, Jonathan J.; Altidor, Lindsay; Barbier, Estelle; Cifani, Carlo; Li, Xuan; Reiner, David J.; Rubio, F. Javier; Hope, Bruce T.; Yang, Yihong; Bossert, Jennifer M.; Shaham, Yavin
Source
Science Advances. 9(2)
Subject
Language
English
ISSN
2375-2548
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, Daun020-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.