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Orbitofrontal cortex and dorsal striatum functional connectivity predicts incubation of opioid craving after voluntary abstinence

Ida Fredriksson and Pei-Jung Tsai

Ida Fredriksson and Pei-Jung Tsai

Hot Off the Press – November 5, 2021

We recently introduced a rat model of incubation (time-dependent increase) of oxycodone craving after voluntary abstinence induced by negative consequences of drug seeking. We used resting-state functional MRI to determine whether longitudinal functional connectivity changes in orbitofrontal cortex (OFC) circuits would predict incubation of oxycodone seeking after cessation of drug self-administration by introducing an electric barrier near the oxycodone-paired lever. We report that opposing functional connectivity changes in OFC with dorsal striatum and related circuits during oxycodone self-administration versus voluntary abstinence predicted incubation of opioid seeking. OFC functional connectivity changes did not predict food seeking, which abated after voluntary abstinence. We propose that functional connectivity changes in OFC-related circuits at different addiction phases can be used to predict opioid relapse vulnerability.

Publication Information

Fredriksson, Ida; Tsai, Pei-Jung; Shekara, Aniruddha; Duan, Ying; Applebey, Sarah V; Lu, Hanbing; Bossert, Jennifer M; Shaham, Yavin; Yang, Yihong

Orbitofrontal cortex and dorsal striatum functional connectivity predicts incubation of opioid craving after voluntary abstinence Journal Article

In: Proc Natl Acad Sci U S A, vol. 118, no. 43, 2021, ISSN: 1091-6490.

Abstract | Links

@article{pmid34675078,
title = {Orbitofrontal cortex and dorsal striatum functional connectivity predicts incubation of opioid craving after voluntary abstinence},
author = {Ida Fredriksson and Pei-Jung Tsai and Aniruddha Shekara and Ying Duan and Sarah V Applebey and Hanbing Lu and Jennifer M Bossert and Yavin Shaham and Yihong Yang},
url = {https://pubmed.ncbi.nlm.nih.gov/34675078/},
doi = {10.1073/pnas.2106624118},
issn = {1091-6490},
year = {2021},
date = {2021-10-01},
urldate = {2021-10-01},
journal = {Proc Natl Acad Sci U S A},
volume = {118},
number = {43},
abstract = {We recently introduced a rat model of incubation of opioid craving after voluntary abstinence induced by negative consequences of drug seeking. Here, we used resting-state functional MRI to determine whether longitudinal functional connectivity changes in orbitofrontal cortex (OFC) circuits predict incubation of opioid craving after voluntary abstinence. We trained rats to self-administer for 14 d either intravenous oxycodone or palatable food. After 3 d, we introduced an electric barrier for 12 d that caused cessation of reward self-administration. We tested the rats for oxycodone or food seeking under extinction conditions immediately after self-administration training (early abstinence) and after electric barrier exposure (late abstinence). We imaged their brains before self-administration and during early and late abstinence. We analyzed changes in OFC functional connectivity induced by reward self-administration and electric barrier-induced abstinence. Oxycodone seeking was greater during late than early abstinence (incubation of oxycodone craving). Oxycodone self-administration experience increased OFC functional connectivity with dorsal striatum and related circuits that was positively correlated with incubated oxycodone seeking. In contrast, electric barrier-induced abstinence decreased OFC functional connectivity with dorsal striatum and related circuits that was negatively correlated with incubated oxycodone seeking. Food seeking was greater during early than late abstinence (abatement of food craving). Food self-administration experience and electric barrier-induced abstinence decreased or maintained functional connectivity in these circuits that were not correlated with abated food seeking. Opposing functional connectivity changes in OFC with dorsal striatum and related circuits induced by opioid self-administration versus voluntary abstinence predicted individual differences in incubation of opioid craving.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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We recently introduced a rat model of incubation of opioid craving after voluntary abstinence induced by negative consequences of drug seeking. Here, we used resting-state functional MRI to determine whether longitudinal functional connectivity changes in orbitofrontal cortex (OFC) circuits predict incubation of opioid craving after voluntary abstinence. We trained rats to self-administer for 14 d either intravenous oxycodone or palatable food. After 3 d, we introduced an electric barrier for 12 d that caused cessation of reward self-administration. We tested the rats for oxycodone or food seeking under extinction conditions immediately after self-administration training (early abstinence) and after electric barrier exposure (late abstinence). We imaged their brains before self-administration and during early and late abstinence. We analyzed changes in OFC functional connectivity induced by reward self-administration and electric barrier-induced abstinence. Oxycodone seeking was greater during late than early abstinence (incubation of oxycodone craving). Oxycodone self-administration experience increased OFC functional connectivity with dorsal striatum and related circuits that was positively correlated with incubated oxycodone seeking. In contrast, electric barrier-induced abstinence decreased OFC functional connectivity with dorsal striatum and related circuits that was negatively correlated with incubated oxycodone seeking. Food seeking was greater during early than late abstinence (abatement of food craving). Food self-administration experience and electric barrier-induced abstinence decreased or maintained functional connectivity in these circuits that were not correlated with abated food seeking. Opposing functional connectivity changes in OFC with dorsal striatum and related circuits induced by opioid self-administration versus voluntary abstinence predicted individual differences in incubation of opioid craving.

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  • https://pubmed.ncbi.nlm.nih.gov/34675078/
  • doi:10.1073/pnas.2106624118

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